Abstract
Melatonin has antitumor activity via several mechanisms including its anti-proliferative and pro-apoptotic effects. Moreover, it has been proven that melatonin in combination with chemotherapeutic agents enhances chemotherapy-triggered apoptosis in several types of cancer. Therefore, this study was intended to evaluate whether melatonin is able to strengthen the anti-cancer potential of different chemotherapeutic drugs in human colorectal adenocarcinoma HT-29 cells. We found that treatment with 20µM cisplatin (CIS) or 1mM 5-fluorouracil (5-FU) for 72h induced a decrease in HT-29 cell viability. Furthermore, 1mMmelatonin significantly (P<0.05) increased the cytotoxic effects of 5-FU. Likewise, simultaneous stimulation with 1mM melatonin and 1mM 5-FU significantly (P<0.05) enhanced the ratio of cells with an overproduction of intracellular reactive oxygen species and substantially augmented the population of apoptotic cells compared to the treatment with 5-FU alone. Nonetheless, melatonin only displayed moderate chemosensitizing effects in CIS-treated HT-29 cells, as suggested by a slight increment in the fraction of early apoptotic cells that was observed only after 48h. Consistently, co-stimulation of HT-29 cells with 20µM CIS or 1mM 5-FU in the presence of 1mM melatonin further increased caspase-3 activation. Apart from this, the cytostatic activity displayed by CIS due to S phase arrest was not affected by concomitant stimulation with melatonin. Overall, our results indicate that melatonin increases the sensitivity of HT-29 cells to 5-FU treatment and, consequently, the indolamine could be potentially applied to colorectal adenocarcinoma treatment as a potent chemosensitizing agent.
Published Version
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