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

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]