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Table 3 Melatonin suppressive effects on various cancers via regulation of ER stress

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 Effect on ER stress Key findings Model Cell line/animal Refs.
Gastric cancer 1, 2, 3 mM
50 mg/kg
Activate Melatonin-mediated inhibition of cancer cell proliferation is induced by the IRE/JNK/Beclin1 signaling activation In vitro, in vivo AGS, SGC-7901 cells
Male BALB/c nude mice
Lung, liver and cervical cancer 2 mM Activate Induced apoptosis by ROS generation and JNK activation In vitro HepG2, A549, HeLa [211]
Hepatocellular carcinoma 10–5 M - enhanced HCC sensitivity to sorafenib through suppressing autophagy In vitro HepG2, 7721, Huh7, LO2 [76]
Colorectal cancer 0–1 mM Activate Induced mitochondria-induced cellular apoptosis In vitro SNUC5/
Hepatoma 10–7-10–3 mM - Melatonin was shown as a novel selective ATF-6 inhibitor that can sensitize human hepatoma cells to ER stress inducing apoptosis In vitro HepG2 [74]
Insulinoma 100 μM 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]
Hepatocellular carcinoma 1 mg/kg/d Activate Activated ER stress and apoptosis In vivo Male Wistar rats [75]
Insulinoma 10, 50 μM - Decreased nuclear and cellular expressions of p85α
Decreased cellular expression of HuD and led to a reduction in cellular insulin level and rise in insulin secretion
In vitro INS-1E [78]
Hepatocellular carcinoma 10–3 M Inhibit Attenuated ER stress-mediated resistance to doxorubicin by downregulating the PI3K/AKT pathway, enhancing CHOP levels and reducing Survivin levels In vitro HepG2, SMMC-7721 [79]
Hepatoma 10–9, 10–7, 10–5, 10–3 μM Activate Sensitized cancer cells to ER stress-mediated apoptosis by downregulating COX-2 expression, enhancing the levels of CHOP and reducing the Bcl-2/Bax ratio In vitro HepG2, HL-7702 [73]