Resveratrol, a tumor‐suppressive compound from grapes, induces apoptosis via a novel mitochondrial pathway controlled by Bcl‐2

SPECIFIC AIMSThe clinical application of the tumor-suppressive agent resveratrol in cancer treatment requires an exact understanding of which molecules sensitize cells to, or antagonize them against, its specific signaling cascade. Bcl-2 is frequently expressed in hematological tumors, is associated with an unfavorable prognosis in some of them, and inhibits the efficacy of cytotoxic agents. Bcl-2 functions may be diverse, but predominantly involve mitochondria. We therefore focused on the mitochondrial signaling pathways induced by resveratrol and potentially counteracted by Bcl-2.PRINCIPAL FINDINGS1. Resveratrol-induced apoptosis is inhibited by Bcl-2To study the role of Bcl-2 in resveratrol-induced apoptosis, we used subclones of the CEM-C7H2 T-ALL cell line, which stably overexpressed Bcl-2. After resveratrol treatment of the vector control cell line, apoptosis was induced in a time-dependent manner. Bcl-2 overexpression protected cells from resveratrol-induced apoptosis even over the extended incubat...