tailieunhanh - Melatonin induces antiproliferative activity through modulation of apoptotic pathway in H-ras oncogene transformed 5RP7 cells

In the present study, cytotoxic and apoptotic effects of melatonin were investigated on H-ras oncogene transformed rat embryo fibroblast 5RP7 cells. Melatonin inhibited cell growth and induced apoptosis in 5RP7 cells. | Turkish Journal of Biology Turk J Biol (2015) 39: 879-887 © TÜBİTAK doi: Research Article Melatonin induces antiproliferative activity through modulation of apoptotic pathway in H-ras oncogene transformed 5RP7 cells 1 2, 1 Ayşe KAPLAN , Gülşen AKALIN ÇİFTÇİ *, Hatice Mehtap KUTLU Department of Biology, Faculty of Science, Anadolu University, Eskişehir, Turkey 2 Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey 1 Received: Accepted/Published Online: Printed: Abstract: In the present study, cytotoxic and apoptotic effects of melatonin were investigated on H-ras oncogene transformed rat embryo fibroblast 5RP7 cells. Melatonin inhibited cell growth and induced apoptosis in 5RP7 cells. We showed inhibition of cell proliferation that was time- and dose-dependent in 5RP7 cells for 24 and 48 h. Melatonin was not toxic in NIH/3T3 primary mouse embryonic fibroblast cells at low doses for 24 and 48 h. The IC50 (380 µM) value of melatonin for 48 h was chosen for advanced assays. The percentages of early/late apoptotic cells to which melatonin (IC50: 380 µM) was administered were increased in 5RP7 cells compared to controls for 48 h. The melatonin treatment resulted in increased caspase-3 activity and reduced the mitochondrial membrane potential in the 5RP7 cells for 48 h. The cell cycle arrest caused by melatonin was observed in G1 and G2 phases in the cell cycle analyses in 5RP7 cells for 48 h. These findings show that melatonin induces cell death and apoptosis in H-ras oncogene transformed 5RP7 cells. Melatonin may be an anticancer agent against H-ras oncogene activated cancer cells. Key words: H-ras oncogene transformed 5RP7 cells, melatonin, apoptosis, caspase-3, cell cycle, mitochondrial membrane potential 1. Introduction Oncogenes are important factors in the carcinogenesis process. Cancer cells may demonstrate an .