Stimulators of immunogenic cell death for cancer therapy: focusing on natural compounds

Amiri, Mina; Molavi, Ommoleila; Sabetkam, Shahnaz; Jafari, Sevda; Montazersaheb, Soheila

doi:10.1186/s12935-023-03058-7

Cancer Cell International

Table 4 Natural agents used in combination therapies to enhance ICD

From: Stimulators of immunogenic cell death for cancer therapy: focusing on natural compounds

Agent	Combination	Cell line	Effect	Ref
Sunitinib	Paclitaxel	MDA-MB-231 cells	Synergistic increase of apoptosis, ICD response and improving DC maturation tumor and immunogenicity	[159]
Curcumin	Irinotecan	CT-26 colon carcinoma cells	Upregulation of ICD hallmarks such as CRT and HMGB1. Enhancing the ICD effect	[137]
	Paclitaxel	MCF-7 breast cancer cells	Improving antitumor impacts of paclitaxel by increasing ROS generation Suppression of paclitaxel resistance through the blockade of P-gp	[138]
	Radiation therapy	Normoxic or hypoxic glioma cells	Increase of radiation-mediated apoptosis, CRT exposure, ATP and HSP70 releases, and ER stress	[152]
	mEHT (Modulated electro-hyperthermia) plus resveratrol	CT-26 colon carcinoma cells	Synergistic upregulation of HSP release and immune responses, that enhances anti-tumor efficacy	[160]
Silibinin	Doxorubicin	CT26 colon cancer cells B16F10 cells 4T1 Breast cancer cells	Synergistic increase of ICD induction by Doxorubicin, and elevates the expression level of CRT, HMGB1, and HSP70. Produce higher antitumor efficacy	[143, 161]
Ginsenoside Rh2	Gemcitabine	Murine pancreatic cancer	Increasing tumor immunogenicity, Reducing the level of immunosuppressive factors	[162]
Ginsenoside Rg3	Photodynamic therapy (PDT)	Glioblastoma cells	Potentiation of the effect of chemotherapy and photoimmunotherapy	[139]
	Gefitinib	NSCLC cells (H1299 and A549)	Sensitization to the treatment with Gefitinib, Enhancing Gefitinib‑mediated tumor cytotoxicity	[163]
	Doxorubicin	4T1 cells	Increasing DOX-induced ICD	[164]
	Quercetin	CT26 and HCT116 cell line	Increasing the effects of Rg3-induced ICD by elevating ROS generation	[153]
	Paclitaxel	BGC-823 gastric cancer cells	Synergistic inhibition of growth of human gastric cancer cells	[165]
Shikonin	Mitoxantrone	B16F10 cells RM1 prostate cancer cells	Improving the effects of therapeutic and cytotoxic agents	[134]
	Doxorubicin	A549 lung cancer cells	Induction of apoptosis, damaging the mitochondrial membrane integrity, decreasing ATP levels, inhibition of glycolysis, and preventing ABC transporter expression	[166]
	Arsenic trioxide	Human HCC cell lines	Synergistic anticancer effects	[167]
Alantolactone	Quercetin	CT26-FL3 cells	Quercetin enhances ICD induction characterized by CRT exposure and HMGB1 release.	80]
Lentinan	Oxaliplatin	EC-109 Esophageal Tumor Cells	Inhibition of tumor proliferation, induction of apoptosis lentinan sensitisize cells by activation of ICD	[168]
Celastrol	Mitoxantrone	desmoplastic melanoma cells	Synergistically inducing ICD	[169]
Plumbagin	Dihydrotanshinone I	Hepatocarcinoma (HCC) cell	Formation of more ROS, inducing ICD	[170]
Digoxin	Cisplatin	B16F10 cells	Induction of ICD via CRT translocation and ATP release	[96]
Docosahexaenoic acid (DHA) marine-based compound	Paclitaxel	MCF-7 cells	Significant inhibition of tumor volume growth Sensitizing tumor cells to ptx	[171]
	Oxaliplatin	HCT116 cells	Promoting oxaliplatin-mediated autophagic cell death by enhancing ER stress	[172]
	Apatinib	MDA-MB-231 cells	Increasing inhibition on cell proliferation and migration	[173]

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