Abstract
The herbal drug khat (Catha edulis Forsk.) is habitually used in Eastern Africa and the Middle East. The pharmacological activity of khat is due to its alkaloid fraction which initiates a rapid release of monoamine neurotransmitters from nerve terminals when ingested. Extracts from khat have been shown to induce cell death caspase-dependent apoptosis in human leukaemia cells. In this study, apoptotic sensitivity is correlated with endogenous protein expression of the anti-apoptogen Bcl-2, as well as transfection enforced over expression of Bcl-2. Exposure of a panel of human leukaemia cell lines to khat extract resulted in the development of similar apoptotic morphotypes. The sensitivity of the cell lines to khat induced apoptosis revealed a trend of inverse correlation with endogenous levels of Bcl-2. Stable or transient transfection of Bcl-2 inhibited khat-induced apoptosis, and the threshold for khat-induced apoptosis was lowered by blocking Bcl-2 synthesis with small interfering RNA. Together, these data suggest Bcl-2 modulation as a possible mechanistic pathway through which khat-induced apoptosis may occur.
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