Skip to main content

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
Mice
[95]
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
[193]
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
[77]
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
[94]
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
[98]
\