Effects of melatonin on the proliferation and cis-diamminedichloroplatinum (CDDP) sensitivity of cultured human ovarian cancer cells.
OBJECTIVE
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.
Futagami
M
M
Department of Obstetrics and Gynecology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Sato
S
S
Sakamoto
T
T
Yokoyama
Y
Y
Saito
Y
Y
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D019098:Telomerase / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D019098:Telomerase; D008550:Melatonin; D002945:Cisplatin