Table 3.

Melatonin suppressive effects on various cancers via regulation of ER 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	[77]
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/ WT	[71]
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]