Quercetin and tamoxifen sensitize human melanoma cells to hyperthermia

Hyperthermia produces regression of human cancer. Because hyperthermia has produced only limited results, attention has focused on searching for subst ances able to sensitize tumour cells to the effects of hyperthermia. The fl avonoid quercetin has been reported to be a hyperthermic sensitizer in ovar ian and uterine cervical tumours and in leukaemia. Quercetin and tamoxifen inhibit melanoma cell growth. We therefore investigated whether quercetin a nd tamoxifen can sensitize M10, M14 and MNT1 human melanoma cells to hypert hermia. We observed that both quercetin and tamoxifen synergize with hypert hermia (42.5 degreesC) in reducing the clonogenic activity of M14 and MNT1 and in inducing apoptotic cell death in all three cell lines. As revealed b y flow cytometric and Northern blot analyses, quercetin and tamoxifen reduc ed heat shock protein-70 expression at both protein and mRNA levels. Our re sults suggest that quercetin and tamoxifen can be usefully combined with hy perthermia in the therapy of recurrent and/or metastatic melanoma. (C) 2001 Lippincott Williams & Wilkins.