Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway

  • Authors:
    • Jun Song
    • Sai-Jun Ma
    • Jian-Hua Luo
    • Hui Zhang
    • Ri-Xiong Wang
    • Hui Liu
    • Li Li
    • Zhi-Guang Zhang
    • Rui-Xiang Zhou
  • View Affiliations

  • Published online on: February 26, 2018     https://doi.org/10.3892/or.2018.6282
  • Pages: 1975-1983
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Abstract

Globally, gastric cancer (GC) is one of the most common types of cancer and the third leading cause of cancer‑related death. In China, gastric and liver cancers have the highest mortality rates. Melatonin, also known as N-acetyl‑5-methoxytryptamine, is a hormone that is produced by the pineal gland in animals and regulates sleep and wakefulness. Melatonin has been shown to inhibit various carcinomas, including GC. There are many different hypotheses to explain the anticancer effects of melatonin, including stimulation of apoptosis, inhibition of cell growth, regulation of anticancer immunity, induction of free-radical scavenging, and the competitive inhibition of estrogen. However, the underlying mechanism by which these effects are elicited remains elusive. The aim of the present study was to investigate the effects of melatonin on human GC cells and determine the underlying molecular mechanism. We treated SGC-7901 GC cells with melatonin and analyzed the resulting protein changes using protein chip technology. Several proteins related to cell apoptosis and proliferation were identified and further tested in SGC-7901 GC cells. We found that melatonin induced cell cycle arrest and the downregulation of CDC25A, phospho-CDC25A (at Ser75), p21 (p21Cip1/p21Waf1) and phospho-p21 (at Thr145). Melatonin also induced upregulation of Bax, downregulation of Bcl-xL, an increase in cleaved caspase-9 level and activation of caspase-3, which confirmed the involvement of the mitochondria in melatonin‑induced apoptosis. Upstream regulators of the above proteins, MDM2, phospho-MDM2 (at Ser166) and AKT, phospho-AKT (at Thr308) were all attenuated by melatonin, which led to an increase in p53. The present study demonstrated that the oncostatic effects of melatonin on SGC-7901 GC cells are mediated via the blockade of the AKT/MDM2 intracellular pathway.
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April-2018
Volume 39 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Song J, Ma S, Luo J, Zhang H, Wang R, Liu H, Li L, Zhang Z and Zhou R: Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway. Oncol Rep 39: 1975-1983, 2018
APA
Song, J., Ma, S., Luo, J., Zhang, H., Wang, R., Liu, H. ... Zhou, R. (2018). Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway. Oncology Reports, 39, 1975-1983. https://doi.org/10.3892/or.2018.6282
MLA
Song, J., Ma, S., Luo, J., Zhang, H., Wang, R., Liu, H., Li, L., Zhang, Z., Zhou, R."Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway". Oncology Reports 39.4 (2018): 1975-1983.
Chicago
Song, J., Ma, S., Luo, J., Zhang, H., Wang, R., Liu, H., Li, L., Zhang, Z., Zhou, R."Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway". Oncology Reports 39, no. 4 (2018): 1975-1983. https://doi.org/10.3892/or.2018.6282