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Aging-US: Proliferation, migration, & invasion of pathways: gallbladder cancer

10-25-2021

Aging-US published "Melatonin inhibits proliferation, migration, and invasion by inducing ROS-mediated apoptosis via suppression of the PI3K/Akt/mTOR signaling pathway in gallbladder cancer cells" which reported that melatonin is an indolic compound mainly secreted by the pineal gland and plays a vital role in the regulation of circadian rhythms and cancer therapy.

However, the effects of melatonin in gallbladder cancer and the related mechanism remain unknown. The results showed that melatonin inhibited growth, migration, and invasion of gallbladder cancer cells. Subsequently, the assays suggested that melatonin significantly induced apoptosis in gallbladder cancer cells and altered the expression of the apoptotic proteins, including Bax, Bcl-2, cytochrome C, cleaved caspase-3, and PARP.

Treatment with N-acetyl-L-cysteine or 740 Y-P remarkably attenuated the antitumor effects of melatonin in NOZ and GBC-SD cells. Finally, melatonin suppressed the growth of GBC-SD cells in an athymic nude mice xenograft model in vivo.

Dr. Xiao-Jing Shi and Dr. Wenlong Zhai said, "Gallbladder cancer is reported to be the most aggressive and common pathological type of biliary tract cancer word widely."

Unfortunately, the majority of gallbladder cancer patients are diagnosed when they are at advanced stages, since patients present with metastasis and other symptoms at a late stage.

Previous studies report that the 5-year survival rate for GBC is 13%, and the median survival time is below 1 year. Therefore, novel drugs and therapeutic targets for inoperable patients with GBC are urgently needed.

The 5-year survival rate for GBC is 13%, and the median survival time is below 1 year

The synthesis and secretion of melatonin are controlled by the light/night clock, meaning that light suppresses melatonin synthesis while darkness stimulates its production. After hydroxylation and decarboxylation, tryptophan synthesizes serotonin and this process is regulated by tryptophan hydroxylase and decarboxylase. Serotonin is then acetylated, methylated, and converted to melatonin in the pineal gland.

Recently, accumulating evidence has revealed that melatonin suppresses tumorigenesis, metastasis, and drug resistance in multiple cancers. By reducing the expression of iNOS and COX-2, melatonin restricts inflammatory damaging effects, thus inhibiting tumor progression in breast cancer. Melatonin disrupts the tumor blood vessel formation in renal adenocarcinoma by decreasing VEGF. The relationship between melatonin and gallbladder cancer has however not been clearly established.

These authors evaluated the inhibitory effects of melatonin on gallbladder cancer cell proliferation.

The Shi/Zhai Research Team concluded in their Aging-US Research Output, "the present study demonstrates that melatonin suppresses proliferation, migration, as well as invasion of gallbladder cancer cells. Mechanistically, in vitro, melatonin promoted ROS-mediated apoptosis of gallbladder cancer cells. Further studies suggest that melatonin suppresses the phosphorylation of the PI3K/Akt/mTOR signaling pathway (Figure 7). Moreover, melatonin also inhibits tumor growth in vivo without obvious toxicity. Overall, melatonin may be an effective and novel candidate for the treatment of gallbladder cancer."

Figure 7. The hypothetical schema of melatonin in gallbladder cancer cells.

Full Text - https://www.aging-us.com/article/203561/text

Correspondence to: Xiao-Jing Shi email: shixiaojing@zzu.edu.cn and Wenlong Zhai email: fcczhaiwl@zzu.edu.cn

Keywords: melatonin, apoptosis, PI3K/Akt, ROS, gallbladder cancer

About Aging-US:

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

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