Abstract
It is a well-known fact that sublethal heating of cells results in development of transient and non-heritable resistance to subsequent heating. This phenomenon is called thermotolerance. The exact mechanism of its induction or its development is not yet understood. Identifying the inhibitors of thermotolerance induction or thermotolerance development may be helpful in delineating the mechanism of thermotolerance, and the clinical use of hyperthermia. Cepharanthin, a membrane active drug, was tested in the present study. At a concentration of 10μg/ml, this drug caused slight change in the slope of the survival curve (Do) of SCK cells heated one time at 44°C. The presence of this drugd uring heat conditioning (1st heating) or in the interval between the 1st and 2nd heating had little effect on the response of cells to the 2nd heating. On the other hand, the presence of cepharanthin during the 2nd heating significantly reduced the Do of cell survival for the 2nd heating (Do=28.5min). Cepharanthin at a dose of 5μg/ml also enhanced the cell killing effect of the 2nd heating of thermotolerant SCK cells, when it was administeredd uring the 2nd heating (Do=46.8 min). Low extra cellular pH (pHe=6.6) during the 2ndh eating reduced the Do of cell survival of thermotolerant cells (Do=45.8min). Cepharanthin at a dose of 5μg/ml, added during the 2nd heating in low pHe, significantlyenhan ced the cell killing effect of the 2nd heating (Do=29.4min).
