Abstract
BackgroundMelatonin has been shown with anticancer property and therapeutic potential for tumors. However, there lacks a systematic study on the molecular pathways of melatonin and its antitumor effects in gastrointestinal carcinomas.MethodsUsing the gene expression profiles of four cancer cell lines from three types of gastrointestinal carcinomas before and after melatonin treatment, including gastric carcinoma (GC), colorectal carcinoma (CRC) and hepatocellular carcinoma (HCC), differentially expressed genes (DEGs) and biological pathways influenced by melatonin were identified. The qRT-PCR analyses were performed to validate the effects of melatonin on 5-FU resistance-related genes in CRC.ResultsThere were 17 pathways commonly altered by melatonin in the three cancer types, including FoxO signaling pathways enriched by the upregulated DEGs and cell cycle signaling pathways enriched by the downregulated DEGs, confirmed the dual role of melatonin to tumor growth, pro-apoptosis and anti-proliferation. DEGs upregulated in the three types of cancer tissues but reversely downregulated by melatonin were commonly enriched in RNA transport, spliceosome and cell cycle signaling pathways, which indicate that melatonin might exert antitumor effects through these pathways. Our results further showed that melatonin can downregulate the expression levels of 5-FU resistance-related genes, such as thymidylate synthase in GC and ATR, CHEK1, BAX and MYC in CRC. The qRT-PCR results demonstrated that melatonin enhanced the sensitivity of CRC 5-FU resistant cells by decreasing the expression of ATR.ConclusionsMelatonin exerts the effects of pro-apoptosis and anti-proliferation on gastrointestinal carcinomas, and might increase the sensitivity of 5-FU in GC and CRC patients.
Highlights
Melatonin has been shown with anticancer property and therapeutic potential for tumors
We further found that the differentially expressed genes (DEGs) upregulated in tumor tissues but downregulated by melatonin in the cell lines were all enriched in RNA transport, spliceosome and cell cycle signaling pathways, which might be the potential targets for cancer therapy
Comparison with the genes related with 5-FU resistance in gastric carcinoma (GC) and CRC Because 5-fluorouracil (5-FU) is a routine chemotherapeutic agent of DNA damage in GC and CRC, we further investigated whether DEGs altered by melatonin are associated with 5-FU resistance
Summary
Melatonin has been shown with anticancer property and therapeutic potential for tumors. A large number of studies have reported that melatonin has anticancer effects on numerous types of tumors, such as liver [10, 11], colon [12], breast [13] and ovarian [14] cancers. These studies mainly highlight its dual role in tumor cells: pro-apoptosis and anti-proliferation, which are the two goals in the control of tumor growth. These in vitro studies only used tumor cell lines for a particular cancer type, and there lacks a systematic study to elucidate the global responsive pathways and the antitumor effects of melatonin’s actions across multiple tumor types
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
