Quercetin and tamoxifen sensitize human melanoma cells to hyperthermia

Abstract

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.

Synergistic effect of hyperthermia and neferine on reverse multidrug resistance in adriamycin-resistant SGC7901/ADM gastric cancer cells

“…However, other studies have proved that hyperthermia can induce or up-regulate mdr-1 gene expression. The mechanism may be contributed to heat shock factor-DNA binding in the promoter region of the mdr-1 gene or activation of p38 [16][17][18][19] . So, further study is necessary to investigate the detailed mechanism why hyperthermia and Nef can inhibit the mdr-1/P-gp expression in these backgrounds.…”

“…Some observations found that hyperthermia can decrease P-gp expression [14,15] . Other researches have proved that hyperthermia can induce or up-regulate mdr-1 gene expression [16][17][18][19] . The different results raise some interesting questions: (1) Does hyperthermia exert an influence on mdr-1/P-gp expression in drug-resistant gastric cancer cells?…”

Potential roles of membrane fluidity and ceramide in hyperthermia and alcohol stimulation of TRAIL apoptosis

“…Depending on cell type and treatments applied, heat shock through the induction of Hsps can protect against the deleterious effects induced, for example, by doxorubicin [20], TNFa [21], TRAIL [22] and CD95 (Fas) [23]. However, in other types of cells, hyperthermia enhances apoptosis induced by radiations [24], Gemcitabin [25], Oxaliplatin [26], Quercetin and Tamoxifen [27]. In T-lymphocytes, heat shock was also found to stimulate apoptosis induced by death receptors pathways such as those triggered by CD95 ligand [28] or TRAIL [29].…”

Late Type Apoptosis and Apoptosis Free Lethal Effect of Quercetin in Human Melanoma

“…6,26) Similarly, the ability of quercetin to induce irreversible contact-independent effects on melanoma-cell growth has not been evaluated to date, since quercetin was kept in the culture media until the time of measurement. 6,7,27,28) These issues were addressed in the present study.…”

“…Apoptosis became significant at concentrations of 200 mm and up, started 24 h after removal of quercetin, and reached a peak after 48 h. In previous studies, apoptosis was measured and detected immediately after ending cell exposure to quercetin, 6,26) but, in those studies, the cells were exposed to quercetin for 24 h. Therefore, it is likely that they detected late rather than immediate-type apoptosis. Similarly, UVB irradiation caused significant increases in apoptosis beginning 24 h after irradiation.…”