Effects of melatonin on the proliferation and cis-diamminedichloroplatinum(CDDP) sensitivity of cultured human ovarian cancer cells

Objectives. In this study, we investigated the antiproliferative effect and telomerase activity of melatonin with or without cis-diamminedichloroplati num (CDDP) on CDDP-sensitive HTOA cells and CDDP-resistant OVCAR-3 cells of cultured human ovarian cancer. Methods. HTOA cells and OVCAR-3 cells were cultured in RPMI-1640 at 37 degr eesC with 5% CO2 for 132 h. To examine the antiproliferative effect of mela tonin, cells were cultured with or without melatonin (10(-12)-10(-6) M) and thereafter counted in a 96-well microplate using the alamarBlue assay. To examine the effect of melatonin and CDDP, cells were divided into group A ( intermittent CDDP, 0.5 mug/ml), group B (intermittent CDDP + melatonin), an d group C (sequential (12-h interval) CDDP/melatonin) and thereafter counte d in a 96-well microplate using the alamarBlue assay. In different series, cells were cultured and treated with either ethanol, melatonin, CDDP, or CD DP + melatonin. After harvest, telomerase activity was semiquantified with a fluorescence-based telomeric repeat amplification protocol (F-TRAP). Results. (1) Melatonin produced no antiproliferative effect on both types o f ovarian cancer cells. (2) Melatonin 10(-6) M induced the antiproliferativ e effect in groups B and C compared with group A in the HTOA cell line. (3) Melatonin 10(-9) M produced the antiproliferative effect in groups B and C compared with group A in the OVCAR-3 cell line. (4) Telomerase activity in the HTOA cell line did not change but, in the OVCAR-3 cell line, was signi ficantly lower in the CDDP + melatonin group compared with the ethanol and CDDP groups. Conclusions. Melatonin enhanced CDDP sensitivity in two ovarian cancer cell lines. Thus, melatonin may improve ovarian cancer chemotherapy. (C) 2001 A cademic Press.