Use of resveratrol to improve the effectiveness of cisplatin and doxorubicin: study in human gynecologic cancer cell lines and in rodent heart.
OBJECTIVE
The purpose of this study was to investigate whether resveratrol adds to the growth inhibitory effects of cisplatin and doxorubicin on ovarian and uterine cancer cells and to evaluate whether resveratrol diminishes the cardiac toxicity of doxorubicin in rodent heart.


METHODS
Human ovarian (OVCAR-3) and uterine (Ishikawa) cancer cells in culture were treated with cisplatin and doxorubicin, respectively, with and without resveratrol; and cell growth and viability were evaluated. Neonatal rat ventricular myocytes received doxorubicin in the presence and absence of resveratrol, and cell viability was evaluated. Mice received doxorubicin +/- resveratrol, and electrocardiograms were evaluated. Data were analyzed with analysis of variance and Scheffe's test.


RESULTS
Resveratrol combined with cisplatin or with doxorubicin demonstrated an additive growth-inhibitory anticancer effect with a left shift of the cisplatin and doxorubicin dose/response curves. Resveratrol increased the viability of neonatal rat ventricular myocytes that were treated with doxorubicin and reduced doxorubicin-induced bradycardia and QTc interval prolongation in mice.


CONCLUSIONS
Resveratrol adds to the growth inhibitory/anticancer activity of cisplatin and doxorubicin in vitro and protects against doxorubicin-induced cardiac toxicity both in vitro and in mice.
Rezk
Youssef A
YA
Department of Obstetrics and Gynecology, Albany Medical College, Albany, NY 12208, USA.
Balulad
Sujata S
SS
Keller
Rebecca S
RS
Bennett
James A
JA
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001919:Bradycardia / Q000139:chemically induced / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced / Q000517:prevention & control; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014594:Uterine Neoplasms / Q000473:pathology* / Q000503:physiopathology
D000972:Antineoplastic Agents, Phytogenic; D002316:Cardiotonic Agents; D013267:Stilbenes; D004317:Doxorubicin; D002945:Cisplatin; D000077185:Resveratrol