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 substances able to sensitize tumour cells to the effects of hyperthermia. The flavonoid quercetin has been reported to be a hyperthermic sensitizer in ovarian and uterine cervical tumours and in leukaemia. Quercetin and tamoxifen inhibit melanoma cell growth. We therefore investigated whether quercetin and tamoxifen can sensitize M10, M14 and MNT1 human melanoma cells to hyperthermia. We observed that both quercetin and tamoxifen synergize with hyperthermia (42.5 degrees C) in reducing the clonogenic activity of M14 and MNT1 and in inducing apoptotic cell death in all three cell lines. As revealed by flow cytometric and Northern blot analyses, quercetin and tamoxifen reduced heat shock protein-70 expression at both protein and mRNA levels. Our results suggest that quercetin and tamoxifen can be usefully combined with hyperthermia in the therapy of recurrent and/or metastatic melanoma.
Piantelli
M
M
Department of Oncology and Neurosciences, 'G. D'Annunzio' University, Chieti, Italy.
Tatone
D
D
Castrilli
G
G
Savini
F
F
Maggiano
N
N
Larocca
L M
LM
Ranelletti
F O
FO
Natali
P G
PG
D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006358:Hot Temperature; D006801:Humans; D006979:Hyperthermia, Induced; D020287:In Situ Nick-End Labeling; D008544:Melanocytes / Q000187:drug effects / Q000473:pathology; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D011794:Quercetin / Q000494:pharmacology* / Q000627:therapeutic use; D012313:RNA / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use; D013696:Temperature; D014407:Tumor Cells, Cultured
D018840:HSP70 Heat-Shock Proteins; D013629:Tamoxifen; D012313:RNA; D011794:Quercetin