Prior Exposure of FM3A Cells to Quercetin Results in Enhanced Cytotoxic and Apoptotic Effects of Hyperthermia

• Published in: Japanese Journal of Hyperthermic Oncology Vol. 16; no. 2; pp. 99 - 106
• Main Authors: NOK, ANDREW, KOSAKA, MITSUO, OTHMAN, TIMOTHY, LEE, JEONG-BEOM, MATSUMOTO, TAKAAKI, GOTO, SHINJI
• Format: Journal Article
• Language: English
• Published: Japanese Society for Thermal Medicine 01.06.2000
• Subjects: apoptosis; cancer; FM3A cells; hyperthermia; quercetin
• ISSN: 0911-2529; 1881-9516; 1881-9516
• DOI: 10.3191/thermalmedicine.16.99

Hyperthermia (HT) cancer treatments have been widely utilised, however, cancer cells develop thermotolerance following exposure to HT, and heat shock proteins (HSPs) are responsible for thermotolerance. A plant flavonoid, quercetin (QCT), has been reported to inhibit heat dependent expression of HSPs. In this study, therefore, the effects of prior exposure to QCT followed by HT on the cytotoxic and apoptotic activities were evaluated in FM3A, mouse breast cancer cells. Treatment of FM3A cells to 10 μM QCT and hyperthermia at 43°C for 1 h (HT) suppressed cell proliferation only in 34% and 55%, respectively and were relatively ineffective. Combination of the two treatments (QCT+HT) synergistically inhibited cell proliferation (90% inhibition). QCT+HT also suppressed clonogenicity (80%), compared to the results of QCT (56%) and HT (41%). Apoptotic cell death occurred after each treatment in a time-dependent manner. There was 4.9 ± 0.7%, 9.6 ± 1.5% and 18.1 ± 4.3% apoptosis after QCT+HT, and 3.2 ± 0.2%, 4.6 ± 0.5% and 8.6 ± 2.8% apoptosis after QCT, 3.4 ± 0.1%, 5.1 ± 0.3% and 10.1 ± 3.1% apoptosis after HT 1, 6 and 24 h post exposure compared to control of 2.0 ± 0.1%. HT or QCT proved ineffective in suppressing cell proliferation or inducing apoptosis. QCT+HT induced an accumulation of cells in G2/M and S phases and a reduction in G0/G1phase. The increased FM3A cell killing by HT after prior exposure to QCT is probably due to suppressed HSPs expression and diminished cellular thermotolerance. QCT may play a useful adjunct role in the hyperthermic treatment of resistant tumor.