Published in Cancer Detection and Prevention 1996; 20(5).

Biomodulation by hyperthermia of topoisomerase ii-targeting drugs in human colorectal cancer cells

K Hidaka MD, Y Hirohashi MD, S Sato MD, T Hisatsugu MD, K Miyazaki MD

AIM: We examined whether cytotoxicity by topoisomerase II-targeting anticancer agents could be biomodulated by hyperthermia in human colon cancer cells. METHODS: WiDr human colon cancer cells were exposed to anticancer drugs for 1h immediately or some interval after heat-treatment. The medium was replaced with fresh medium at 37 degrees Celsius, and the dishes were incubated to allow colony formation. The expression of topoisomerase II (Topo II) were assayed by Western blots and Northern blots analysis after the hyperthermia. RESULTS: Both topoisomerase II contents and topoisomerase II activity were more significantly increased in WiDr cells 3 to 12 hr later after heat stress at 43 degrees Celsius for 1 hr, in comparison with those appearing immediately after the heat stress. Cytotoxicity by VP-16 was most significantly enhanced 3 to 12 hr after exposure to 43 degrees Celsius for 1 hr, but no synergistic effect was observed when the drug was administered immediately after the heat stress. A combination of VM-26 with heat stress, but not that of a topoisomerase I-targeting agent, camptothecin derivative (CPT-11), or vincristine, caused synergistic effect on the cytotoxicity of WiDr cells. CONCLUSION: We found delayed enhancement of the cytotoxicity of topoisomerase II inhibitors, as well as delayed increment of the target enzymatic level in the cell, after exposure of human colon cancer cells to hyperthermia. Also, a new evidence on the molecular mechanism of Topo II expression after hyperthermia will be discussed.

KEY WORDS: Biomodulation, Hyperthermia, Topo II.

Paper presented at the International Symposium on the Impact of Cancer Biotechnology on Diagnostic and Prognostic Indicators; Nice, France; October 26 - 28, 1996; in the section on Chemotherapy.

http://www.cancerprev.org/Journal/Issues/20/5/505/1554