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Cytotoxicity of synthetic derivatives against breast cancer and multi-drug resistant breast cancer cell lines: a literature-based perspective study

Abstract

Cancer is the second most killer worldwide causing millions of people to lose their lives every year. In the case of women, breast cancer takes away the highest proportion of mortality rate than other cancers. Due to the mutation and resistance-building capacity of different breast cancer cell lines against conventional therapies, this death rate is on the verge of growth. New effective therapeutic compounds and treatment method is the best way to look out for in this critical time. For instance, new synthetic derivatives/ analogues synthesized from different compounds can be a ray of hope. Numerous synthetic compounds have been seen enhancing the apoptosis and autophagic pathway that directly exerts cytotoxicity towards different breast cancer cell lines. To cease the ever-growing resistance of multi-drug resistant cells against anti-breast cancer drugs (Doxorubicin, verapamil, tamoxifen) synthetic compounds may play a vital role by increasing effectivity, showing synergistic action. Many recent and previous studies have reported that synthetic derivatives hold potentials as an effective anti-breast cancer agent as they show great cytotoxicity towards cancer cells, thus can be used even vastly in the future in the field of breast cancer treatment. This review aims to identify the anti-breast cancer properties of several synthetic derivatives against different breast cancer and multi-drug-resistant breast cancer cell lines with their reported mechanism of action and effectivity.

Introduction

Cancer is typically a heterogeneous disease and one of the second dominant causes of morbidity and mortality around the globe [1, 2]. This disease revolves around unnatural cell proliferation which may or may not invade the other parts of the body. Among all the cancer types, breast cancer is most deadly for women and also contributes to the highest mortality rate when compared to other types [3,4,5,6,7]. According to World Health Organization (WHO) breast cancer is very persistent in women, affecting about 2.3 million each year. In 2020, approximately 685,000 women died from this disease [8]. Estrogen receptor beta (ERβ) has been marked as a possible origin of developing breast cancer and around 60% of breast cancer is hormone-dependent, relying on estrogen for growth [3, 9, 10]. Abnormality and irregularity in the normal cell cycle along with obstructed apoptosis signaling pathway is the fundamental cause for breast cancer progression [11,12,13]. A subtype of breast cancer investigated as triple-negative breast cancer (TNBC) is a result of a shortfall of expression of estrogen receptor alpha/progesterone receptor [9, 14, 15].

As for the treatment’s concern, radiation therapy, chemotherapy, hormone therapy, and targeted therapy are often used alongside surgery for early-stage patients [16,17,18]. Patients with metastatic disease are also treated the same way with systemic therapy which recently included immunotherapy [18]. Most of these therapies incorporate apoptosis or programmed cell death to instigate the anti-breast cancer activity throughout development, differentiation, tumor cell detection, and in response to specific cytotoxicity of molecules or compounds [19,20,21,22]. This programmed cell death follows an intrinsic or extrinsic pathway that comes with a series of occurrences including the altered ratio of Bax/Bcl-2 protein, activated caspases, and bifurcated poly [ADP-ribose] polymerase (PARP-1) enzyme [21, 23,24,25,26,27]. Generation of reactive oxygen species (ROS) and formation of nitric oxide (NO) also leads to p53 activation which results in DNA damage of cancer cells [28,29,30,31]. Autophagy, a cellular homeostasis mechanism may also contribute to breast cancer cell death where autophagosomes amalgamate with the lysosome to establish autophagolysosome during starvation and stress [32]. PARP-1 enlivening and LC3-II protein marker urges autophagic cell death [33, 34]. Figure 1 summarizes the mechanisms involved in breast cancer cell death.

Fig. 1
figure1

Mechanisms of breast cancer cell death. CYP cytochrome, ER endoplasmic reticulum, hAP-2γ human transcription factor activation protein-2 γ, PARP-1 poly [ADP-ribose] polymerase 1, RONS reactive oxygen and nitrogen species, VEGF vascular endothelial growth factor

Considering the complexity of the disease and the paucity of an effective chemotherapeutic agent, breast cancer besides other cancers has drawn the attention of researchers. Many of these researches have pointed towards chemotherapeutic agents that have been procured from natural or synthetic origin [21]. A slight modification in the structure of the natural compound or by the synthesis of specific analogues worthwhile activities is seen in the case of cancer therapy. Paclitaxel, vinca alkaloids, camtothecin, and etoposide are some of the synthetic derivatives vastly used for cancer therapy originally attained from natural sources [35]. Synthetically derived substances for cancer therapy are highly being studied in a hope that they might tame the unexpected and unavoidable side-effects originated by chemotherapeutic drugs [36]. A Wyrębska, K Gach, U Lewandowska, K Szewczyk, E Hrabec, J Modranka, R Jakubowski, T Janecki, J Szymański and A Janecka [37] reported the anti-breast cancer activity of synthetically derived α-methylene-δ-lactones on hormone-independent MDA-MB-231, hormone-dependent MCF-7 cell lines through intrinsic apoptotic pathway activation, cancer cell migration suppression, and invasion. Synthetic vitamins, curcuminoids, isoflavones, chromenes are also seemed to have anti-breast cancer activity when tested on different cell lines [38,39,40,41,42,43,44].

Another vital road-blocker is the development of resistance that calls for never-ending neediness for new therapeutics [45,46,47]. Multi-drug resistance (MDR), the main fundamental cause behind chemotherapy failure may develop due to some complex mechanism including transporter-mediated efflux, over-expression of efflux transporters: P-glycoprotein (ABCB-1/P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated proteins (MRPs) present on the cell membrane [48,49,50,51,52,53,54,55]. Efflux transporters effectively pump out drugs that are meant to create cytotoxicity in the cell. As a result, the intracellular concentration of that specific drug fall. MDR cancer cells containing efflux or ATP-binding cassette (ABC) transporters can significantly interact or deliver a plethora of anticancer compounds using the hydrophobic vacuum cleaner mode where the hydrophobic compounds get attach to the MDR-1 on account of their hydrophobicity for efflux [56]. In the case of a pump-independent mechanism, the cellular anti-apoptotic defense system activation develops resistance toward chemotherapeutic agents by upregulating BCL2 gene [57]. Evidence shows that synthetically derived compounds effectively exert cytotoxicity on MDR cancer cells. Zhou et al. [58], stated that synthetically derived β-amino ester inhibits P-gp activity by lowering mitochondrial membrane potentials and ATP levels on MCF-7 cell line. The enhanced antitumor effect might be attributed to PHP-mediated lysosomal escape and drug efflux inhibition.Various other studies show a similar effect on different tested cell lines.

Traditionally available chemotherapeutic agents may develop undesirable side effects and sometimes may also lack efficacy. So, new and advanced sources are in need that may counterbalance the present difficulties. In this study, the cytotoxic effect of different synthetic derivatives on normal and MDR cell lines is thoroughly discussed. This review set the sights on drawing the attention of researchers to conduct more advanced level analysis on the cytotoxicity of these synthetically derived analogues.

Methodology

A search (till February 2021) was done in the following databases: PubMed, Science Direct, MedLine, and Google Scholar with the keyword ‘Synthetic derivative’, paring with ‘against breast cancer cell line/ multi-drug-resistant breast cancer cell lines or cytotoxicity on breast cancer/ multidrug-resistant cell line. No language restrictions were imposed. Articles were assessed for information about the synthetic derivatives, breast cancer cell lines, multi-drug-resistant breast cancer cell lines, test results, and possible mechanisms of action.

Inclusion criteria

The following inclusion criteria were adopted:

  1. 1.

    Studies with synthetic derivatives/analogues from various sources.

  2. 2.

    Studies carried out in vivo, in vitro, or ex vivo on breast cancer cells/ multi-drug-resistant breast cancer cells.

  3. 3.

    Studies with or without activity mechanism.

Exclusion criteria

The following exclusion criteria were adopted:

  1. 1.

    Titles and/or abstract not meeting the inclusion criteria, duplication of data.

  2. 2.

    Synthetic derivatives with other studies obscuring the current subject of interest.

Findings

Among the vast pieces of evidence, some randomly selected published articles found in the databases that contain screening reports on synthetic derivatives acting against breast cancer/ MDR cell-line have been summarized below:

Cytotoxicity of synthetic derivatives on different breast cancer cell lines

Synthetic derivatives in a similar manner tonatural substances follow apoptosis and autophagic pathways to inhibit the growth and activity of breast cancer cells. Other than that inhibition of cell proliferation, induction of cell-cycle arrest may occur. AM Oliveira Rocha, F Severo Sabedra Sousa, V Mascarenhas Borba, SM T, J Guerin Leal, OE Dorneles Rodrigues, GF M, L Savegnago, T Collares and F Kömmling Seixas [59] reported the anti-breast cancer activity of synthetic azidothymidine (AZT) derivatives containing tellurium (Te) on MDA-MB-231 cell-line using MTT assay. The derived compounds 7 m and 7r showed an inhibitory effect on the breast cancer cell-line through lowering cell proliferation, initiating cell-cycle arrest in the S phase in the absence of the apoptosis process. Subsequently, the synthetic drug pair, piperidinyl-diethylstilbestrol (DES), pyrrolidinyl-DES exhibits cytotoxicity on MCF-7 cell-line in both in vivo and in vitro assay. In the case of the in vitro study, these drugs manifest cytotoxicity on shrimp larvae at LC50 19.7 ± 0.95 and 17.6 ± 0.4 μg/mL respectively. In vivo cell inhibition is seen by ceasing G0/G1-phase of the MCF-7 cell cycle following ED50 value 7.9 ± 0.38 and 15.6 ± 1.3 μg/mL [36].

The induction of apoptotic pathways can be an effective course of action to inhibit cancer cells. Studies reported a heap of incidences where apoptosis effectively took part in breast cancer cell destruction [38, 60, 61]. Kheirollahi et al. [39] reported the anti-breast activity of synthetic benzochromene derivatives on 3 different breast cancer cells (MCF-7, MDA-MB-231, and T-47D) where the derivatives participate in ROS and NO production through direct modification of proteins, lipids, and DNA that induces apoptosis in cancer cell lines. To that add this, synthetic oleanolic acid derivative HIMOXOL induced apoptotic pathway by activating caspase-8, caspase-3, and PARP-1 protein, elevating the ratio of Bax/Bcl-2 protein level, triggering microtubule-associated protein LC3-II expression, and upregulating bectin 1 on MDA-MB-231 cell-line at IC50 value 7.33 ± 0.79 μM [62].

Autophagic pathway activation by synthetic derivatives is also marked as a potential solution in the case of cancer cell inhibition. Synthetic β-nitrostyrene derivative, CYT-Rx20 shows inhibitory activity on MCF-7, MDA-MB-231, and ZR75-1 cell-line with IC50 value 0.81 ± 0.04, 1.82 ± 0.05, and 1.12 ± 0.06 μg/mL respectively. The cytotoxic mechanism behind this can be illustrated as arrested cancer cells at the G2/M phase, decreased cell viability by activating caspase cascade, increased PARP cleavage, and γ-H2AX expression as well as induced autophagy by upregulation of Bectin-1, autophagy related 5 (ATG5), LC-3, and formation of ROS [63].

[3H] Thymidine is often incorporated into the daughter strands of DNA during the mitotic cell division process. As [3H] thymidine may directly calculate the proliferation so inhibition of incorporation often points towards anti-proliferative activity [64]. Synthetic derivatives effectively inhibit [3H] thymidine incorporation into the breast cancer cell to promote activity. Wyrębska et al. [65] stated that synthetic derivative MZ-6 inhibited incorporation of [3H] thymidine dose-dependently alongside induced apoptosis into MCF-7, MDA-MB-231 breast cancer cell line. Furthermore, Synthetic caffeic acid phenethyl ester (CAPE) isolated from propolis shows a similar result when tested upon MCF-7 at IC50 5 μg/mL [66].

Table 1 summarizes the synthetic derivatives acting against different breast cancer cell lines and Fig. 2 represents the chemical structures of these compounds.

Table 1 Synthetic derivatives acting against different breast cancer cell lines
Fig. 2
figure2

Chemical structure of some synthetic derivatives that acting against different breast cancer cell lines

Cytotoxicity of synthetic derivatives on different multi-drug resistant (MDR) cancer cell lines

Resistance against drugs used for a specific purpose can be a hugely troublesome matter when it comes to the treatment of a serious disease like cancer. Not only in the case of treatment but also in the case of the development of new therapeutics, “Multi-drug resistance” can be an invisible obstacle in pharmacology [83]. The resistance of tumor cells towards chemotherapeutic agents, leading to the failure of cancer treatment can be defined as MDR [45, 46]. MDR of cancer cells during chemotherapy should be associated with a different type of mechanisms that are including enhanced efflux of drugs, genetic factors (gene mutations, amplifications, and epigenetic alterations), growth factors, increased DNA repair capacity, and also elevated metabolism of xenobiotics (Fig. 3). In the case of breast cancer, advancements in treatment and prevention have taken place over the last decade but MDR has been witnessed as the main roadblock [48]. In recent years, the use of different synthetically derived substances has been seen effective against MDR breast cancer cells.

Fig. 3
figure3

Mechanisms of chemotherapeutic drug resistance in cancer cells

One of the major reasons for MDR is the over-expression of P-gp, a protein encoded by the MDR-1 gene belonging to the ABC membrane transporters family. HB Xu, L Li and GQ Liu [84] reported that a synthetic derivative Guggulsterone shows an MDR-reversal effect, a valuable adjunct to chemotherapy. Increased intracellular accumulation of Doxorubicin, an anti-breast cancer drug, results in the expression Guggulsterone in both MRP1 and P-gp in drug-resistant MCF-7 cells. Again sphingosine stereoisomers, another synthetic compound reduces basal phosphorylation of the P-gp ion in MCF-7/ADR cells, suggesting inhibition of protein kinase C (PKC)-mediated phosphorylation of P-gp [85]. 1,4-Dihydropyridines (DHPs) 3-pyridyl methyl carboxylate and alkyl carboxylate moieties inhibited rhodamine 123 efflux showing the mechanism of MDR reversal in P-gp transporter modulation. Lowered resistance of MES-SA/DX5 to doxorubicin also exerted the anti-tumor effect in MCF-7ADR cells [86].

Additionally, induction of apoptosis and autophagy can be effective ways to look out for. Genistein at IC50 value 73.89 µM showed an anti-tumor effect against MCF-7 cells. Induced cell-cycle arrest and apoptosis caused by genistein treatment strongly inhibits HER2/neu but not MDR-1 expression at both the mRNA and protein levels. Geinstein acts synergistically with doxorubicin by increasing intracellular accumulation of doxorubicin and suppressed HER2/neu expression [87]. M Distefano, G Scambia, C Ferlini, C Gaggini, R De Vincenzo, A Riva, E Bombardelli, I Ojima, A Fattorossi, PB Panici, et al. [88] stated that a series of14β-hydroxy-10-deacetylbaccatin III (14-OH-DAB) analogues induce cell cycle block at G2/M in a concentration-dependent manner. G1/G2 ratio, measured as the amount of cell block correlates significantly (p < 0.001) with apoptosis, evaluated in the sub-G1 region. This incident suggests G2/M-blocked cells underwent apoptosis in both MDA-MBA-231, MCF-7ADRr cells.

Table 2 summarizes the synthetic derivatives acting against multi-drugresistant MCF-7 cell-line and Fig. 4 represents the chemical structures of these compounds.

Table 2 Synthetic derivatives acting against multi-drugresistant MCF-7 cell-line
Fig. 4
figure4

Chemical structure of some synthetic derivatives that acting against multi-drug resistant MCF-7 cell-line

Conclusion

The most common type of cancer is breast cancer for women worldwide, and approximately 25% of all female malignancies that have a high appearance in most of the developed countries. The second leading cause of death due to cancer among females in the world is breast cancer. The mortality rate of breast cancer is higher than the other types of cancer. Recent studies give evidence that the synthetic derivatives give effective action against breast cancer cell lines and also give action against multi drug resistant in MCF-7 cell lines. This review offers a very large amount of data on the mechanism of action of synthetic derivatives on multidrug resistance and could provide the basis for the discovery of new drugs against breast cancer. Multi drug resistance of cancer cells during chemotherapy it has been associated with a different type of mechanisms that are including enhanced efflux of drugs, genetic factors (gene mutations, amplifications, and epigenetic alterations), growth factors, increased DNA repair capacity, and also elevated metabolism of xenobiotics. For this reason, further studies required for the future purpose to know more about synthetic derivatives activity against breast cancer and multi drug resistance breast cancer cell lines.

Availability of data and materials

Not applicable.

References

  1. 1.

    McGuire S: World Cancer Report 2014. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO Press, 2015. Adv Nutr 2016, 7(2):418–419.

  2. 2.

    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    PubMed  Google Scholar 

  3. 3.

    Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212–36.

    PubMed  Google Scholar 

  4. 4.

    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.

    PubMed  Google Scholar 

  5. 5.

    Satsangi A, Roy SS, Satsangi RK, Tolcher AW, Vadlamudi RK, Goins B, Ong JL. Synthesis of a novel, sequentially active-targeted drug delivery nanoplatform for breast cancer therapy. Biomaterials. 2015;59:88–101.

    CAS  PubMed  Google Scholar 

  6. 6.

    Lin KL, Tsai PC, Hsieh CY, Chang LS, Lin SR. Antimetastatic effect and mechanism of ovatodiolide in MDA-MB-231 human breast cancer cells. Chem Biol Interact. 2011;194(2–3):148–58.

    CAS  PubMed  Google Scholar 

  7. 7.

    Keshtgar M, Davidson T, Pigott K, Falzon M, Jones A. Current status and advances in management of early breast cancer. Int J Surg. 2010;8(3):199–202.

    CAS  PubMed  Google Scholar 

  8. 8.

    WHO: Breast cancer. World Health Organization (WHO) Report 2021, 26 March 2021.

  9. 9.

    Yu XL, Jing T, Zhao H, Li PJ, Xu WH, Shang FF. Curcumin inhibits expression of inhibitor of DNA binding 1 in PC3 cells and xenografts. Asian Pac J Cancer Prev. 2014;15(3):1465–70.

    PubMed  Google Scholar 

  10. 10.

    Parsai S, Keck R, Skrzypczak-Jankun E, Jankun J. Analysis of the anticancer activity of curcuminoids, thiotryptophan and 4-phenoxyphenol derivatives. Oncol Lett. 2014;7(1):17–22.

    CAS  PubMed  Google Scholar 

  11. 11.

    Liu H, Liu YZ, Zhang F, Wang HS, Zhang G, Zhou BH, Zuo YL, Cai SH, Bu XZ, Du J. Identification of potential pathways involved in the induction of cell cycle arrest and apoptosis by a new 4-arylidene curcumin analogue T63 in lung cancer cells: a comparative proteomic analysis. Mol Biosyst. 2014;10(6):1320–31.

    CAS  PubMed  Google Scholar 

  12. 12.

    Solary E, Dubrez L, Eymin B. The role of apoptosis in the pathogenesis and treatment of diseases. Eur Respir J. 1996;9(6):1293–305.

    CAS  PubMed  Google Scholar 

  13. 13.

    Favaloro B, Allocati N, Graziano V, Di Ilio C, De Laurenzi V. Role of apoptosis in disease. Aging (Albany NY). 2012;4(5):330–49.

    CAS  Google Scholar 

  14. 14.

    Bourgeois-Daigneault MC, St-Germain LE, Roy DG, Pelin A, Aitken AS, Arulanandam R, Falls T, Garcia V, Diallo JS, Bell JC. Combination of Paclitaxel and MG1 oncolytic virus as a successful strategy for breast cancer treatment. Breast Cancer Res. 2016;18(1):83.

    PubMed  PubMed Central  Google Scholar 

  15. 15.

    Kreike B, van Kouwenhove M, Horlings H, Weigelt B, Peterse H, Bartelink H, van de Vijver MJ. Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res. 2007;9(5):R65.

    PubMed  PubMed Central  Google Scholar 

  16. 16.

    Richie RC, Swanson JO. Breast cancer: a review of the literature. J Insur Med. 2003;35(2):85–101.

    PubMed  Google Scholar 

  17. 17.

    Satija A, Ahmed SM, Gupta R, Ahmed A, Rana SP, Singh SP, Mishra S, Bhatnagar S. Breast cancer pain management - a review of current & novel therapies. Indian J Med Res. 2014;139(2):216–25.

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    Street W. Breast Cancer Facts & Figures 2019–2020. Am Cancer Soc. 2019;1:1–38.

    Google Scholar 

  19. 19.

    Huang P, Robertson LE, Wright S, Plunkett W. High molecular weight DNA fragmentation: a critical event in nucleoside analogue-induced apoptosis in leukemia cells. Clin Cancer Res. 1995;1(9):1005–13.

    CAS  PubMed  Google Scholar 

  20. 20.

    Safavi M, Esmati N, Ardestani SK, Emami S, Ajdari S, Davoodi J, Shafiee A, Foroumadi A. Halogenated flavanones as potential apoptosis-inducing agents: synthesis and biological activity evaluation. Eur J Med Chem. 2012;58:573–80.

    CAS  PubMed  Google Scholar 

  21. 21.

    Lu Y, Mahato RI. Pharmaceutical perspectives of cancer therapeutics. New York: Springer Science & Business Media; 2009.

    Google Scholar 

  22. 22.

    Xie K, Huang S. Contribution of nitric oxide-mediated apoptosis to cancer metastasis inefficiency. Free Radic Biol Med. 2003;34(8):969–86.

    CAS  PubMed  Google Scholar 

  23. 23.

    D’Arcy MS. Cell death: a review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int. 2019;43(6):582–92.

    PubMed  Google Scholar 

  24. 24.

    Lowe SW, Lin AW. Apoptosis in cancer. Carcinogenesis. 2000;21(3):485–95.

    CAS  PubMed  Google Scholar 

  25. 25.

    Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495–516.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2010;22(2):124–31.

    CAS  PubMed  Google Scholar 

  27. 27.

    Timmer JC, Salvesen GS. Caspase substrates. Cell Death Differ. 2007;14(1):66–72.

    CAS  PubMed  Google Scholar 

  28. 28.

    Kannan K, Jain SK. Oxidative stress and apoptosis. Pathophysiology. 2000;7(3):153–63.

    CAS  PubMed  Google Scholar 

  29. 29.

    Sinha K, Das J, Pal PB, Sil PC. Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch Toxicol. 2013;87(7):1157–80.

    CAS  PubMed  Google Scholar 

  30. 30.

    Brown GC, Cooper CE. Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett. 1994;356(2–3):295–8.

    CAS  PubMed  Google Scholar 

  31. 31.

    Sikora AG, Gelbard A, Davies MA, Sano D, Ekmekcioglu S, Kwon J, Hailemichael Y, Jayaraman P, Myers JN, Grimm EA, et al. Targeted inhibition of inducible nitric oxide synthase inhibits growth of human melanoma in vivo and synergizes with chemotherapy. Clin Cancer Res. 2010;16(6):1834–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Fulda S, Gorman AM, Hori O, Samali A. Cellular stress responses: cell survival and cell death. Int J Cell Biol. 2010;2010:214074.

    PubMed  PubMed Central  Google Scholar 

  33. 33.

    Mizushima N, Yoshimori T, Levine B. Methods in mammalian autophagy research. Cell. 2010;140(3):313–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Muñoz-Gámez JA, Rodríguez-Vargas JM, Quiles-Pérez R, Aguilar-Quesada R, Martín-Oliva D, de Murcia G. Menissier de Murcia J, Almendros A, Ruiz de Almodóvar M, Oliver FJ: PARP-1 is involved in autophagy induced by DNA damage. Autophagy. 2009;5(1):61–74.

    PubMed  Google Scholar 

  35. 35.

    Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol. 2005;100(1–2):72–9.

    CAS  PubMed  Google Scholar 

  36. 36.

    Badisa RB, Darling-Reed SF, Joseph P, Cooperwood JS, Latinwo LM, Goodman CB. Selective cytotoxic activities of two novel synthetic drugs on human breast carcinoma MCF-7 cells. Anticancer Res. 2009;29(8):2993–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Wyrębska A, Gach K, Lewandowska U, Szewczyk K, Hrabec E, Modranka J, Jakubowski R, Janecki T, Szymański J, Janecka A. Anticancer Activity of New Synthetic α-Methylene-δ-Lactones on Two Breast Cancer Cell Lines. Basic Clin Pharmacol Toxicol. 2013;113(6):391–400.

    PubMed  Google Scholar 

  38. 38.

    Ali NM, Yeap SK, Abu N, Lim KL, Ky H, Pauzi AZM, Ho WY, Tan SW, Alan-Ong HK, Zareen S, et al. Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells. Cancer Cell Int. 2017;17:30.

    PubMed  PubMed Central  Google Scholar 

  39. 39.

    Kheirollahi A, Pordeli M, Safavi M, Mashkouri S, Naimi-Jamal MR, Ardestani SK. Cytotoxic and apoptotic effects of synthetic benzochromene derivatives on human cancer cell lines. Naunyn Schmiedebergs Arch Pharmacol. 2014;387(12):1199–208.

    CAS  PubMed  Google Scholar 

  40. 40.

    Cameron IL, Munoz J, Barnes CJ, Hardman WE. High dietary level of synthetic vitamin E on lipid peroxidation, membrane fatty acid composition and cytotoxicity in breast cancer xenograft and in mouse host tissue. Cancer Cell Int. 2003;3(1):3.

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Davis DD, Díaz-Cruz ES, Landini S, Kim YW, Brueggemeier RW. Evaluation of synthetic isoflavones on cell proliferation, estrogen receptor binding affinity, and apoptosis in human breast cancer cells. J Steroid Biochem Mol Biol. 2008;108(1–2):23–31.

    CAS  PubMed  Google Scholar 

  42. 42.

    Pordeli M, Nakhjiri M, Safavi M, Ardestani SK, Foroumadi A. Anticancer effects of synthetic hexahydrobenzo [g]chromen-4-one derivatives on human breast cancer cell lines. Breast Cancer. 2017;24(2):299–311.

    PubMed  Google Scholar 

  43. 43.

    Rahmani-Nezhad S, Safavi M, Pordeli M, Ardestani SK, Khosravani L, Pourshojaei Y, Mahdavi M, Emami S, Foroumadi A, Shafiee A. Synthesis, in vitro cytotoxicity and apoptosis inducing study of 2-aryl-3-nitro-2H-chromene derivatives as potent anti-breast cancer agents. Eur J Med Chem. 2014;86:562–9.

    CAS  PubMed  Google Scholar 

  44. 44.

    Alipour E, Mousavi Z, Safaei Z, Pordeli M, Safavi M, Firoozpour L, Mohammadhosseini N, Saeedi M, Ardestani SK, Shafiee A, et al. Synthesis and cytotoxic evaluation of some new[1,3]dioxolo[4,5-g]chromen-8-one derivatives. Daru. 2014;22(1):41.

    PubMed  PubMed Central  Google Scholar 

  45. 45.

    Gottesman MM. How cancer cells evade chemotherapy: sixteenth Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res. 1993;53(4):747–54.

    CAS  PubMed  Google Scholar 

  46. 46.

    Liscovitch M, Lavie Y. Cancer multidrug resistance: a review of recent drug discovery research. IDrugs. 2002;5(4):349–55.

    CAS  PubMed  Google Scholar 

  47. 47.

    Boer R, Gekeler V. Chemosensitizers in tumor therapy: new compounds promise better efficacy. Drugs of the Future. 1995;20(5):499–510.

    Google Scholar 

  48. 48.

    Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL, et al. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science. 2009;323(5922):1718–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Zahreddine H, Borden KL. Mechanisms and insights into drug resistance in cancer. Front Pharmacol. 2013;4:28.

    PubMed  PubMed Central  Google Scholar 

  50. 50.

    Ling V. Multidrug resistance: molecular mechanisms and clinical relevance. Cancer Chemother Pharmacol. 1997;40(Suppl):S3-8.

    CAS  PubMed  Google Scholar 

  51. 51.

    Choudhuri S, Klaassen CD. Structure, function, expression, genomic organization, and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) efflux transporters. Int J Toxicol. 2006;25(4):231–59.

    CAS  PubMed  Google Scholar 

  52. 52.

    Ozben T. Mechanisms and strategies to overcome multiple drug resistance in cancer. FEBS Lett. 2006;580(12):2903–9.

    CAS  PubMed  Google Scholar 

  53. 53.

    Palmeira A, Vasconcelos MH, Paiva A, Fernandes MX, Pinto M, Sousa E. Dual inhibitors of P-glycoprotein and tumor cell growth: (re)discovering thioxanthones. Biochem Pharmacol. 2012;83(1):57–68.

    CAS  PubMed  Google Scholar 

  54. 54.

    Lemos C, Jansen G, Peters GJ. Drug transporters: recent advances concerning BCRP and tyrosine kinase inhibitors. Br J Cancer. 2008;98(5):857–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Chen KG, Sikic BI. Molecular pathways: regulation and therapeutic implications of multidrug resistance. Clin Cancer Res. 2012;18(7):1863–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Higgins CF, Gottesman MM. Is the multidrug transporter a flippase? Trends Biochem Sci. 1992;17(1):18–21.

    CAS  PubMed  Google Scholar 

  57. 57.

    McCubrey JA, Steelman LS, Kempf CR, Chappell WH, Abrams SL, Stivala F, Malaponte G, Nicoletti F, Libra M, Bäsecke J, et al. Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways. J Cell Physiol. 2011;226(11):2762–81.

    CAS  PubMed  Google Scholar 

  58. 58.

    Zhou M, Zhang X, Xie J, Qi R, Lu H, Leporatti S, Chen J, Hu Y. pH-Sensitive Poly(β-amino ester)s Nanocarriers Facilitate the Inhibition of Drug Resistance in Breast Cancer Cells. Nanomaterials (Basel). 2018;8:11.

    Google Scholar 

  59. 59.

    Oliveira Rocha AM. Severo Sabedra Sousa F, Mascarenhas Borba V, Guerin Leal J, Dorneles Rodrigues OE, M GF, Savegnago L, Collares T, Kömmling Seixas F: Evaluation of the effect of synthetic compounds derived from azidothymidine on MDA-MB-231 type breast cancer cells. Bioorg Med Chem Lett. 2020;30(17):127365.

    CAS  PubMed  Google Scholar 

  60. 60.

    Chen Y, Qin Y, Li L, Chen J, Zhang X, Xie Y. Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis. Biol Pharm Bull. 2017;40(10):1686–92.

    CAS  PubMed  Google Scholar 

  61. 61.

    Stumm S, Meyer A, Lindner M, Bastert G, Wallwiener D, Gückel B. Paclitaxel treatment of breast cancer cell lines modulates Fas/Fas ligand expression and induces apoptosis which can be inhibited through the CD40 receptor. Oncology. 2004;66(2):101–11.

    CAS  PubMed  Google Scholar 

  62. 62.

    Lisiak N, Paszel-Jaworska A, Bednarczyk-Cwynar B, Zaprutko L, Kaczmarek M, Rybczyńska M. Methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate (HIMOXOL), a synthetic oleanolic acid derivative, induces both apoptosis and autophagy in MDA-MB-231 breast cancer cells. Chem Biol Interact. 2014;208:47–57.

    CAS  PubMed  Google Scholar 

  63. 63.

    Hung AC, Tsai CH, Hou MF, Chang WL, Wang CH, Lee YC, Ko A, Hu SC, Chang FR, Hsieh PW, et al. The synthetic β-nitrostyrene derivative CYT-Rx20 induces breast cancer cell death and autophagy via ROS-mediated MEK/ERK pathway. Cancer Lett. 2016;371(2):251–61.

    CAS  PubMed  Google Scholar 

  64. 64.

    Hu VW, Black GE, Torres-Duarte A, Abramson FP. 3H-thymidine is a defective tool with which to measure rates of DNA synthesis. Faseb j. 2002;16(11):1456–7.

    CAS  PubMed  Google Scholar 

  65. 65.

    Wyrębska A, Szymański J, Gach K, Piekielna J, Koszuk J, Janecki T, Janecka A. Apoptosis-mediated cytotoxic effects of parthenolide and the new synthetic analog MZ-6 on two breast cancer cell lines. Mol Biol Rep. 2013;40(2):1655–63.

    PubMed  Google Scholar 

  66. 66.

    Grunberger D, Banerjee R, Eisinger K, Oltz EM, Efros L, Caldwell M, Estevez V, Nakanishi K. Preferential cytotoxicity on tumor cells by caffeic acid phenethyl ester isolated from propolis. Experientia. 1988;44(3):230–2.

    CAS  PubMed  Google Scholar 

  67. 67.

    Bardon S, Vignon F, Montcourrier P, Rochefort H. Steroid receptor-mediated cytotoxicity of an antiestrogen and an antiprogestin in breast cancer cells. Cancer Res. 1987;47(5):1441–8.

    CAS  PubMed  Google Scholar 

  68. 68.

    Peng F, Meng CW, Zhou QM, Chen JP, Xiong L. Cytotoxic Evaluation against Breast Cancer Cells of Isoliquiritigenin Analogues from Spatholobus suberectus and Their Synthetic Derivatives. J Nat Prod. 2016;79(1):248–51.

    CAS  PubMed  Google Scholar 

  69. 69.

    Polkowski K, Popiołkiewicz J, Krzeczyński P, Ramza J, Pucko W, Zegrocka-Stendel O, Boryski J, Skierski JS, Mazurek AP, Grynkiewicz G. Cytostatic and cytotoxic activity of synthetic genistein glycosides against human cancer cell lines. Cancer Lett. 2004;203(1):59–69.

    CAS  PubMed  Google Scholar 

  70. 70.

    Rusin A, Zawisza-Puchałka J, Kujawa K, Gogler-Pigłowska A, Wietrzyk J, Switalska M, Głowala-Kosińska M, Gruca A, Szeja W, Krawczyk Z, et al. Synthetic conjugates of genistein affecting proliferation and mitosis of cancer cells. Bioorg Med Chem. 2011;19(1):295–305.

    CAS  PubMed  Google Scholar 

  71. 71.

    Thuaud F, Bernard Y, Türkeri G, Dirr R, Aubert G, Cresteil T, Baguet A, Tomasetto C, Svitkin Y, Sonenberg N, et al. Synthetic analogue of rocaglaol displays a potent and selective cytotoxicity in cancer cells: involvement of apoptosis inducing factor and caspase-12. J Med Chem. 2009;52(16):5176–87.

    CAS  PubMed  Google Scholar 

  72. 72.

    Vargas Casanova Y, Rodríguez Guerra JA, Umaña Pérez YA, Leal Castro AL, Almanzar Reina G, García Castañeda JE, Rivera Monroy ZJ. Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines. Molecules. 2017;22:10.

    Google Scholar 

  73. 73.

    Alonso R, Gomis H, Taddei A, Sajo C. Cytostatic and Cytotoxic Activity of Synthetic Diterpene Derivatives Obtained from (-)-Kaur-9(11), 16-Dien-19-Oic Acid Against Human Cancer Cell Lines. Lett Drug Des Discov. 2005;2(4):255–9.

    CAS  Google Scholar 

  74. 74.

    Sukhramani PS, Sukhramani PS, Desai SA, Suthar MP. In-vitro cytotoxicity evaluation of novel N-substituted bis-benzimidazole derivatives for anti-lung and anti-breast cancer activity. Ann Biol Res. 2011;2(1):51–9.

    CAS  Google Scholar 

  75. 75.

    Rattanaburee T, Thongpanchang T, Wongma K, Tedasen A, Sukpondma Y, Graidist P. Anticancer activity of synthetic (±)-kusunokinin and its derivative (±)-bursehernin on human cancer cell lines. Biomed Pharmacother. 2019;117:109115.

    CAS  PubMed  Google Scholar 

  76. 76.

    Lei J, Li X, Gong XJ, Zheng YN. Isolation, synthesis and structures of cytotoxic ginsenoside derivatives. Molecules. 2007;12(9):2140–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. 77.

    Li W, Zhang H, Nie M, Wang W, Liu Z, Chen C, Chen H, Liu R, Baloch Z, Ma K. A novel synthetic ursolic acid derivative inhibits growth and induces apoptosis in breast cancer cell lines. Oncol Lett. 2018;15(2):2323–9.

    PubMed  Google Scholar 

  78. 78.

    Liu MC, Yang SJ, Jin LH, Hu DY, Xue W, Song BA, Yang S. Synthesis and cytotoxicity of novel ursolic acid derivatives containing an acyl piperazine moiety. Eur J Med Chem. 2012;58:128–35.

    CAS  PubMed  Google Scholar 

  79. 79.

    Thomet FA, Pinyol P, Villena J, Espinoza LJ, Reveco PG. Cytotoxic thiocarbamate derivatives of boldine. Nat Prod Commun. 2010;5(10):1587–90.

    CAS  PubMed  Google Scholar 

  80. 80.

    Khaledi H, Alhadi AA, Yehye WA, Ali HM, Abdulla MA, Hassandarvish P. Antioxidant, cytotoxic activities, and structure-activity relationship of gallic acid-based indole derivatives. Arch Pharm (Weinheim). 2011;344(11):703–9.

    CAS  Google Scholar 

  81. 81.

    Elmegeed GA, Khalil WK, Mohareb RM, Ahmed HH, Abd-Elhalim MM, Elsayed GH. Cytotoxicity and gene expression profiles of novel synthesized steroid derivatives as chemotherapeutic anti-breast cancer agents. Bioorg Med Chem. 2011;19(22):6860–72.

    CAS  PubMed  Google Scholar 

  82. 82.

    Sala M, Chimento A, Saturnino C, Gomez-Monterrey IM, Musella S, Bertamino A, Milite C, Sinicropi MS, Caruso A, Sirianni R, et al. Synthesis and cytotoxic activity evaluation of 2,3-thiazolidin-4-one derivatives on human breast cancer cell lines. Bioorg Med Chem Lett. 2013;23(17):4990–5.

    CAS  PubMed  Google Scholar 

  83. 83.

    Ahamed A, Arif IA, Mateen M, Surendra Kumar R, Idhayadhulla A. Antimicrobial, anticoagulant, and cytotoxic evaluation of multidrug resistance of new 1,4-dihydropyridine derivatives. Saudi J Biol Sci. 2018;25(6):1227–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84.

    Xu HB, Li L, Liu GQ. Reversal of multidrug resistance by guggulsterone in drug-resistant MCF-7 cell lines. Chemotherapy. 2011;57(1):62–70.

    CAS  PubMed  Google Scholar 

  85. 85.

    Sachs CW, Ballas LM, Mascarella SW, Safa AR, Lewin AH, Loomis C, Carroll FI, Bell RM, Fine RL. Effects of sphingosine stereoisomers on P-glycoprotein phosphorylation and vinblastine accumulation in multidrug-resistant MCF-7 cells. Biochem Pharmacol. 1996;52(4):603–12.

    CAS  PubMed  Google Scholar 

  86. 86.

    Shekari F, Sadeghpour H, Javidnia K, Saso L, Nazari F, Firuzi O, Miri R. Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells. Eur J Pharmacol. 2015;746:233–44.

    CAS  PubMed  Google Scholar 

  87. 87.

    Xue JP, Wang G, Zhao ZB, Wang Q, Shi Y. Synergistic cytotoxic effect of genistein and doxorubicin on drug-resistant human breast cancer MCF-7/Adr cells. Oncol Rep. 2014;32(4):1647–53.

    CAS  PubMed  Google Scholar 

  88. 88.

    Distefano M, Scambia G, Ferlini C, Gaggini C, De Vincenzo R, Riva A, Bombardelli E, Ojima I, Fattorossi A, Panici PB, et al. Anti-proliferative activity of a new class of taxanes (14beta-hydroxy-10-deacetylbaccatin III derivatives) on multidrug-resistance-positive human cancer cells. Int J Cancer. 1997;72(5):844–50.

    CAS  PubMed  Google Scholar 

  89. 89.

    Crawford KW, Bittman R, Chun J, Byun HS, Bowen WD. Novel ceramide analogues display selective cytotoxicity in drug-resistant breast tumor cell lines compared to normal breast epithelial cells. Cell Mol Biol. 2003;49(7):1017–23.

    CAS  PubMed  Google Scholar 

  90. 90.

    Csonka A, Kincses A, Nové M, Vadas Z, Sanmartín C, Domínguez-Álvarez E, Spengler G. Selenoesters and selenoanhydrides as novel agents against resistant breast cancer. Anticancer Res. 2019;39(7):3777–83.

    CAS  PubMed  Google Scholar 

  91. 91.

    Lee YJ, Won AJ, Lee J, Jung JH, Yoon S, Lee BM, Kim HS. Molecular mechanism of SAHA on regulation of autophagic cell death in tamoxifen-resistant MCF-7 breast cancer cells. Int J Med Sci. 2012;9(10):881–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Liu R, Zhang Y, Chen Y, Qi J, Ren S, Xushi MY, Yang C, Zhu H, Xiong D. A novel calmodulin antagonist O-(4-ethoxyl-butyl)-berbamine overcomes multidrug resistance in drug-resistant MCF-7/ADR breast carcinoma cells. J Pharm Sci. 2010;99(7):3266–75.

    CAS  PubMed  Google Scholar 

  93. 93.

    Qi J, Wang S, Liu G, Peng H, Wang J, Zhu Z, Yang C. Pyronaridine, a novel modulator of P-glycoprotein-mediated multidrug resistance in tumor cells in vitro and in vivo. Biochem Biophys Res Commun. 2004;319(4):1124–31.

    CAS  PubMed  Google Scholar 

  94. 94.

    Wang X, Wang C, Zhang L, Li Y, Wang S, Wang J, Yuan C, Niu J, Wang C, Lu G. Salvianolic acid A shows selective cytotoxicity against multidrug-resistant MCF-7 breast cancer cells. Anticancer Drugs. 2015;26(2):210–23.

    CAS  PubMed  Google Scholar 

  95. 95.

    Xu HB, Li L, Fu J, Mao XP, Xu LZ. Reversion of multidrug resistance in a chemoresistant human breast cancer cell line by β-elemene. Pharmacology. 2012;89(5–6):303–12.

    CAS  PubMed  Google Scholar 

  96. 96.

    Dönmez Y, Akhmetova L, İşeri ÖD, Kars MD, Gündüz U. Effect of MDR modulators verapamil and promethazine on gene expression levels of MDR1 and MRP1 in doxorubicin-resistant MCF-7 cells. Cancer Chemother Pharmacol. 2011;67(4):823–8.

    PubMed  Google Scholar 

  97. 97.

    Zheng X, Li D, Zhao C, Wang Q, Song H, Qin Y, Liao L, Zhang L, Lin Y, Wang X. Reversal of multidrug resistance in vitro and in vivo by 5-N-formylardeemin, a new ardeemin derivative. Apoptosis. 2014;19(8):1293–300.

    CAS  PubMed  Google Scholar 

  98. 98.

    Merzouki A, Buschmann MD, Jean M, Young RS, Liao S, Gal S, Li Z, Slilaty SN. Adva-27a, a novel podophyllotoxin derivative found to be effective against multidrug resistant human cancer cells. Anticancer Res. 2012;32(10):4423–32.

    CAS  PubMed  Google Scholar 

  99. 99.

    Fu LW, Zhang YM, Liang YJ, Yang XP, Pan QC. The multidrug resistance of tumour cells was reversed by tetrandrine in vitro and in xenografts derived from human breast adenocarcinoma MCF-7/adr cells. Eur J Cancer. 2002;38(3):418–26.

    CAS  PubMed  Google Scholar 

  100. 100.

    Li J, Yao QY, Xue JS, Wang LJ, Yuan Y, Tian XY, Su H, Wang SY, Chen WJ, Lu W, et al. Dopamine D2 receptor antagonist sulpiride enhances dexamethasone responses in the treatment of drug-resistant and metastatic breast cancer. Acta Pharmacol Sin. 2017;38(9):1282–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. 101.

    Deng X, Qiu Q, Yang B, Wang X, Huang W, Qian H. Design, synthesis and biological evaluation of novel peptides with anti-cancer and drug resistance-reversing activities. Eur J Med Chem. 2015;89:540–8.

    CAS  PubMed  Google Scholar 

  102. 102.

    Li JM, Zhang W, Su H, Wang YY, Tan CP, Ji LN, Mao ZW. Reversal of multidrug resistance in MCF-7/Adr cells by codelivery of doxorubicin and BCL2 siRNA using a folic acid-conjugated polyethylenimine hydroxypropyl-β-cyclodextrin nanocarrier. Int J Nanomedicine. 2015;10:3147–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. 103.

    Wu L, Xu J, Yuan W, Wu B, Wang H, Liu G, Wang X, Du J, Cai S. The reversal effects of 3-bromopyruvate on multidrug resistance in vitro and in vivo derived from human breast MCF-7/ADR cells. PLoS ONE. 2014;9(11):e112132.

    PubMed  PubMed Central  Google Scholar 

  104. 104.

    Li Y, Zhang HB, Huang WL, Li YM. Design and synthesis of tetrahydroisoquinoline derivatives as potential multidrug resistance reversal agents in cancer. Bioorg Med Chem Lett. 2008;18(12):3652–5.

    CAS  PubMed  Google Scholar 

  105. 105.

    Giordano C, Catalano S, Panza S, Vizza D, Barone I, Bonofiglio D, Gelsomino L, Rizza P, Fuqua SA, Andò S. Farnesoid X receptor inhibits tamoxifen-resistant MCF-7 breast cancer cell growth through downregulation of HER2 expression. Oncogene. 2011;30(39):4129–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. 106.

    Park JH, Ahn MY, Kim TH, Yoon S, Kang KW, Lee J, Moon HR, Jung JH, Chung HY, Kim HS. A new synthetic HDAC inhibitor, MHY218, induces apoptosis or autophagy-related cell death in tamoxifen-resistant MCF-7 breast cancer cells. Invest New Drugs. 2012;30(5):1887–98.

    CAS  PubMed  Google Scholar 

  107. 107.

    Wang K, Ramji S, Bhathena A, Lee C, Riddick DS. Glutathione S-transferases in wild-type and doxorubicin-resistant MCF-7 human breast cancer cell lines. Xenobiotica. 1999;29(2):155–70.

    CAS  PubMed  Google Scholar 

  108. 108.

    Yu ST, Chen TM, Chern JW, Tseng SY, Chen YH. Downregulation of GSTpi expression by tryptanthrin contributing to sensitization of doxorubicin-resistant MCF-7 cells through c-jun NH2-terminal kinase-mediated apoptosis. Anticancer Drugs. 2009;20(5):382–8.

    CAS  PubMed  Google Scholar 

  109. 109.

    Zhao J, Zeng D, Liu Y, Luo Y, Ji S, Li X, Chen T. Selenadiazole derivatives antagonize hyperglycemia-induced drug resistance in breast cancer cells by activation of AMPK pathways. Metallomics. 2017;9(5):535–45.

    CAS  PubMed  Google Scholar 

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Acknowledgements

These are to the Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology Univerity, Gopalganj (8100), Dhaka, Bangladesh.

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The work was supervised by MM, MB, JS-R, MTI. Project administration was performed by JS-R, MB, and MTIm. Final draft of the work was by SS, ICB, RVB, Md.MR, MM, JS-S, JS-R and MTI. All authors read and approved the final manuscript.

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Correspondence to Javad Sharifi-Rad or Monica Butnariu.

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Sharmin, S., Rahaman, M.M., Martorell, M. et al. Cytotoxicity of synthetic derivatives against breast cancer and multi-drug resistant breast cancer cell lines: a literature-based perspective study. Cancer Cell Int 21, 612 (2021). https://doi.org/10.1186/s12935-021-02309-9

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Keywords

  • Synthetic derivatives
  • Breast cancer cell line
  • MDR breast cancer cell line
  • Cytotoxicity