BUTYRATE ATTENUATES BCLXL EXPRESSION IN HUMAN FIBROBLASTS AND ACTS INSYNERGY WITH IONIZING-RADIATION TO INDUCE APOPTOSIS

Ionizing radiation is a poor inducer of apoptosis in many cell types. In this study we investigated what effect the differentiation agent bu tyrate had on the cellular levels of the apoptosis regulators BCL2, BC LXL and BAX and on radiation-induced apoptosis. It was found that buty rate 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 a n increased induction of apoptosis in cells irradiated with ionizing r adiation. Butyrate also acted in synergy with ultraviolet (UV) light a nd cisplatin to induce apoptosis in human fibroblasts. Radiosensitizat ion was obtained when butyrate was added before andlor after irradiati on, although the combination of treatment both before and after irradi ation was the most effective. Our results suggest that butyrate acts i n synergy with ionizing radiation, UV light and cisplatin to induce ap optosis, perhaps by lowering the level of the apoptosis antagonist BCL XL in cells. (C) 1998 by Radiation Research Society.