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-diamminedichloroplatinum (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 degrees C with 5% CO(2) for 132 h. To examine the antiproliferative effect of melatonin, 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 microg/ml), group B (intermittent CDDP + melatonin), and group C (sequential (12-h interval) CDDP/melatonin) and thereafter counted in a 96-well microplate using the alamarBlue assay. In different series, cells were cultured and treated with either ethanol, melatonin, CDDP, or CDDP + 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 of ovarian cancer cells. (2) Melatonin 10(-6) M induced the antiproliferative 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 significantly 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. Copyright 2001 Academic Press.