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Table 4 The effect of melatonin on autophagy machinery in recently reported findings

From: An updated review of mechanistic potentials of melatonin against cancer: pivotal roles in angiogenesis, apoptosis, autophagy, endoplasmic reticulum stress and oxidative stress

Cancer Melatonin dose/concentration Autophagy-related targets Effect on autophagy Key findings Model Cell line Refs.
Lung, liver and cervical cancer 2 mM LC3 Activate Induced apoptosis by ROS generation and JNK activation In vitro HepG2, A549, HeLa [124]
Glioblastoma 1 mM Beclin 1, LC3-II Activate Autophagy disruption stimulated the melatonin-mediated apoptosis in cancer cells In vitro A172, U87-MG [97]
Uterine leiomyoma 25 mg/kg
0.1, 0.5, 1, 1.5, 2 mM
Beclin1 and LC3 Activate Reduced tumor growth and proliferation In vivo, in vitro ELT3 cells, orthotopic uterine leiomyoma mouse model [192]
Hepatocellular carcinoma 10−5_ 10–3 M PERK-ATF4-Beclin1 pathway Inhibit enhanced HCC sensitivity to sorafenib through suppressing autophagy Human - [76]
Colorectal cancer 10 μM LC3-II Activate Induced interplay of apoptosis, autophagy, and senescence In vitro HCT116 [171]
Clear cell renal cell carcinoma 200 mg/kg
0.5, 1, 2 μM
PGC1A, UCP1, LC3‐II Activate Melatonin/PGC1A/UCP1 promoted tumor slimming and repressed tumor progression through initiating autophagy and lipid browning In vivo, in vitro HK2, 786‐O, A498, Caki‐1, and ACHN cells
Neuroblastoma 0.1‐ 10 nM
40‐80 mg/kg
LC3II Activate Promoted cancer cell differentiation through activation of hyaluronan synthase 3-mediated mitophagy In vivo, in vitro N2a
N2a‐allografted nude mice
Head and neck squamous cell carcinoma 0.1, 0.5, 1, 1.5 mM ATG12-ATG5 Activate Induced intracellular ROS In vitro Cal-27, SCC-9 [93]
Hepatocellular carcinoma 1 mM mTOR, Beclin-1 Activate Decreased cisplatin-mediated cell death by a counter-balance between the roles of apoptotic- and autophagy-related proteins In vitro HepG2 [101]
Hepatocellular carcinoma 2 mM Beclin-1, p62, LC3II, LAMP-2 Activate Ceramide metabolism regulated apoptotic and autophagy cell death mediated by melatonin In vitro HepG2 [96]
Neuroblastoma 1 μM Beclin‐1, LC3‐II Activate Enhanced autophagic activity by the SIRT1 signaling In vitro SH‐SY5Y [194]
Gastric cancer 10−4 M LC3 Activate Hyperbaric oxygen sensitized cancer cells to melatonin-mediated apoptosis In vitro SGC7901 [151]
Colon cancer 1 mg/kg Beclin-1, LC3B-II/LC3B-I ratio, p62 Inhibit Decreased autophagy by improving oxidative stress and inflammation In vivo Male Swiss Albino mice [99]
Glioblastoma 1 mM LC3, Beclin-1 Activate Inhibited tumor bulk proliferation, and enhanced chemotherapy effects In vitro Glioblastoma-initiating cells [195]
Oral cancer 0.5–2 mM LC3-II Activate Decreased drug resistance, and induced autophagy and apoptosis In vitro SAS, SCC9, SASV16, SASV32, SCC9V16, SCC9V32 [139]
Gastric cancer 50 mg/kg
1, 2, 3 mM
p62, Beclin-1, LC3A/B-II Activate Melatonin-mediated inhibition of cancer cell proliferation is induced by the IRE/JNK/Beclin1 signaling activation In vivo, in vitro AGS, SGC-7901
Male BALB/c nude mice
Hepatocellular carcinoma 10, 20 mg/kg
100 μM
Beclin-1, LC3-I/LC3-II Activate Induced protective autophagy preventing hepatoma cells from undergoing apoptosis In vitro, in vivo H22 [196]
Insulinoma 100 μM LC3II Activate Melatonin-induced insulin synthesis involved autophagy and EDC3 protein in rat insulinoma cells and subsequently resulted in a resuction in intracellular production of insulin In vitro INS-1E [72]
Chriocarcinoma 1 mM LC3B Inhibit Modulated autophagy and the Nrf2 pathway in normal vs. tumor trophoblast cells, being cytoprotective in normal cells whilst enhancing apoptosis in tumoral trophoblast cells In vitro BeWo [197]
Cervical cancer 1 mM JNK/Parkin Inhibit Sensitized cancer cells to cisplatin-mediated apoptosis by suppression of JNK/Parkin/mitophagy pathways In vitro HeLa [100]
Head and neck squamous cell carcinoma 0.1, 0.5 or 1 mM
300 mg/kg
LC3-II, Nix Activate Enhanced ROS production, increased apoptosis and mitophagy, and could be used as an adjuvant agent with rapamycin In vitro, in vivo Cal-27, SCC-9
Harlan Sprague–Dawley mice
Tongue squamous cell carcinoma 0, 0.5, 1, 2 mM
100 mg/kg
LC3, ATG7 Activate Suppression of MT2-TFE3-dependent autophagy enhanced melatonin-mediated apoptosis In vitro, in vivo Cal27, SCC9
Male athymic nude mice