Abstract
Hyperthermia (HT) in combination with antiproliferative drugs (APDs) had proved efficacious in various cancers, although efficacy vary among compounds and cancer types. Presently there are few data that compares antiproliferative efficacies among APDs under hyperthermic conditions. We therefore selected four commonly used APDs (quercetin, verapamil, paclitaxel and doxorubicin) and compared their antitumor effects when combined with 43 °C heat. FM3A murine breast cancer cells were exposed to each APD for 1 h followed by exposure to 43 °C heat for 1 additional hour and processed for the effects of : 1) each drug, 2) heat and 3) combination of each drug and 43°C HT 1, 6 and 24 h post exposure. The overall effects (i.e., arrested proliferation, clonogenic efficiency and apoptosis) was determined. Prior exposure of FM3A cells to each of the APD followed by 43 °C produced greater anti-tumor effects (suppressed cell proliferation, reduced clonogenic efficiency and increased apoptotic cell death) compared to APD or HT alone. Apoptotic cell death occurred in a time-dependent manner. Among the APDs, anti-tumor efficacies vary in the order doxorubicin > verapamil > paclitaxel > quercetin. It was concluded that exposure of cancer cells to APD and heat simultaneously may offer a better anti-tumor benefit than exposure to APD alone, and the antiproliferative benefits derived from thermochemotherapy may differ significantly from one drug to another.
