title: AKT serine/threonine protein kinase modulates bufalin-triggered intrinsic             pathway of apoptosis in CAL 27 human oral cancer cells.
abstract: Bufalin has been reported to induce apoptosis in a variety of cancers but             little is demonstrated in oral squamous cell carcinoma (OSCC) cells. The present             study investigated the inhibition of proliferation, cell cycle arrest and apoptotic             effects of bufalin in CAL 27 human oral cancer cells. Bufalin inhibited the growth             of CAL 27 cells in a concentration-dependent manner and an IC50 value of bufalin             was about 125 nM for 24 h treatment using the MTT assay. Moreover, the cell cycle             distribution was arrested at the G0/G1 phase in CAL 27 cells after bufalin exposure.             Upon bufalin stimulation, the expression of Bcl-2 was significantly decreased             while that of cytochrome c, Apaf-1 and AIF was increased compared to the control             group by western blot analysis. An increase in the expression of the active form             of caspases was found in bufalin-treated cells, and the caspase activities were             also elevated. Bufalin-triggered apoptosis was blocked by specific inhibitors             of caspase-9 (z-LEHD-fmk) and caspase-3 (z-DEVD-fmk), respectively. In contrast,             CAL 27 cells overexpressing constitutively active AKT (CAL 27/CA-AKT) were exposed             to bufalin at different concentrations, and cell growth remained unchanged. Bufalin             exhibited minimal apoptotic effects on CAL 27/CA-AKT cells. Taken together, bufalin             induced G0/G1 phase arrest and provoked the intrinsic apoptotic pathway via AKT             activation in CAL 27 cells. Our data suggest that bufalin could be potentially             efficacious in the treatment of oral cancer in the future.
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, ROC.
authors.forename: Shih-Chang
authors.initials: SC
authors.lastname: Tsai
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Lu
authors.forename: Chao-Ying
authors.initials: CY
authors.lastname: Lee
authors.forename: Yung-Chang
authors.initials: YC
authors.lastname: Lin
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
authors.forename: Sheng-Chu
authors.initials: SC
authors.lastname: Kuo
authors.forename: Sakae
authors.initials: S
authors.lastname: Amagaya
authors.forename: Fei-Na
authors.initials: FN
authors.lastname: Chen
authors.forename: Michael Yuanchien
authors.initials: MY
authors.lastname: Chen
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Chan
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002018:Bufanolides / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D002018:Bufanolides; D019253:Proto-Oncogene Proteins c-bcl-2; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053453:Caspase 9; C022777:bufalin