Butyrate Attenuates BCLX L Expression in Human Fibroblasts and Acts in Synergy with Ionizing Radiation to Induce Apoptosis

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Abstract
Ionizing radiation is a poor inducer of apoptosis in many cell types. In this study we investigated what effect the differentiation agent butyrate had on the cellular levels of the apoptosis regulators BCL2, BCLXL and BAX and on radiation-induced apoptosis. It was found that butyrate significantly lowered the level of the apoptosis antagonist BCLXL in a time-and dose-dependent manner in diploid human fibroblasts. The reduction of the level of BCLXL protein by butyrate correlated with an increased induction of apoptosis in cells irradiated with ionizing radiation. Butyrate also acted in synergy with ultraviolet (UV) light and cisplatin to induce apoptosis in human fibroblasts. Radiosensitization was obtained when butyrate was added before andlor after irradiation, although the combination of treatment both before and after irradiation was the most effective. Our results suggest that butyrate acts in synergy with ionizing radiation, UV light and cisplatin to induce apoptosis, perhaps by lowering the level of the apoptosis antagonist BCLXL in cells. (C) 1998 by Radiation Research Society.