title: Bufalin induces apoptosis through activation of both the intrinsic and             extrinsic pathways in human bladder cancer cells.
abstract: Bufalin, a major digoxin-like immunoreactive component of the Chinese medicine             Chansu, is prepared from toad venom. This compound has been shown to exert a potential             for anticancer activity against various human cancer cell lines in vitro. However,             the detailed molecular mechanisms of its induction of apoptosis are still unclear.             In this study, we investigated the apoptosis-inducing effect of bufalin in T24             human bladder cancer cells. Our data revealed that bufalin treatment resulted             in a concentration-response growth inhibition of T24 cells by inducing cell cycle             arrest at the G2/M phase and apoptosis, as evidenced by formation of apoptotic             bodies, chromatin condensation and accumulation of cells in the sub-G1 phase.             Apoptosis induction of T24 cells by bufalin showed correlation with proteolytic             activation of caspase-3, -8 and -9, and concomitant degradation of poly (ADP-ribose)             polymerases, and collapse of the mitochondria membrane potential. In addition,             bufalin treatment resulted in an increase of the Bax/Bcl-2 (or Bcl-xL) ratio and             caused down-regulation of inhibitor of apoptosis protein (IAP) family members.             The increase in apoptosis by bufalin treatment was also associated with up-regulation             of death receptor-related factors. Our data indicate that the growth inhibitory             effects of bufalin occur through blockade of the G2/M phase, and that these cancer             cells do not enter cell cycle progression and die through apoptosis via both intrinsic             and extrinsic pathways.
authors: Department of Biochemistry, College of Oriental Medicine, Research                     Institute of Oriental Medicine, Dong-Eui University, Busan 614-052, Republic                     of Korea.
authors: Su-Hyun
authors: SH
authors: Hong
authors: Yung Hyun
authors: YH
authors: Choi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002018:Bufanolides / Q000494:pharmacology*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002018:Bufanolides; C022777:bufalin