He effect of melatonin on chemotherapeutic activity of paclitaxel on HCT-116-human colon cell line

Colorectal cancer is one of the most prevalent cancer type. Combinatorial treatment strategies are important field of cancer research. Paclitaxel (PTX) is a chemotherapy medication used to treat huge number of types of cancer. However, the resistance to the PTX treatment restrict its use in the clinics. Melatonin (MTN) is mainly produced by pineal gland. Besides its well-known function as the regulation of the circadian rhythm, anticancer effects have been indicated. The aim of this study is to determine the effect of MTN on PTX treatment. In our study, human colorectal carcinoma cell line, HCT-116 was used. The toxicity, the dose and the duration of exposure of PTX and MTN were determined using the water-soluble tetrazolium-1 (WST-1) colorimetric cell proliferation assay kit. HCT-116 cells were treated with different combinations of MTN, PTX and MTN + PTX for 24 hours. Apoptosis and necrosis findings were obtained by flow cytometry using MEBCYTO Apoptosis Kit. Statistical analysis was performed using Kruskal Wallis and Mann Whitney U tests with helping of SPSS 18 software program. Five different doses and two different exposure times were tried for MTN and PXL, and the dose of MTN was 500 μM and PXL was 50 nM (p <0.05). Exposure time is 24 hours for both substances. When the increasing doses of MTN were applied together with PXL, it was observed that the cell viability decreased compared to the group treated with PXL (p <0.05). While 50 nM and 24 hour PXL administration increased apoptosis, addition of 24-hour MTN to this application resulted in an increase in apotosis (p <0.05). Compatible with the apoptosis data, the addition of MTN in necrosis results increased the effect of PXL (p < 0.01). Our results suggest that MTN potentiates the chemotherapeutic effect of PTX in a dose dependent manner.