Essential role of voltage —dependent anion channel （VDAC） in mitochondrial permeability transition and cytochrome C release induced by arsenic trioxide

Arsenic trioxide (As2O3) has been used clinically for treating cancers by inducing apoptosis of cancer cells. The molecular mechanisms and its targets for As2Os to induce apoptosis remain elusive. Here, we investigated the molecular mechanisms underlying mitochondrial apoptosis induced by As2O3. Exposure of isolated mouse liver mitochondria with As2Oa elicited permeability transition pore (PTP) opening, cytochrome c (cyt c) release (CCR) and collapse of mitochondrial membrane potential (△(?)m). PTP inhibitors cyclosporin A (CsA), Bongkrekic acid (BA) and Bcl-XL prevented these mitochondrial apoptosis and CCR induced by As2C>3. We, for the first time, provided evidence suggesting that As2O3 induces mi-