title: Caudatin induces caspase-dependent apoptosis in human glioma cells with involvement of mitochondrial dysfunction and reactive oxygen species generation.
abstract: Caudatin as one species of C-21 steroidal from Cynanchum bungei decne displays potential anticancer activity. However, the underlying mechanisms remain elusive. In the present study, the growth suppressive effect and mechanism of caudatin on human glioma U251 and U87 cells were evaluated in vitro. The results indicated that caudatin significantly inhibited U251 and U87 cell growth in both a time- and dose-dependent manner. Flow cytometry analysis revealed that caudatin-induced cell growth inhibition was achieved by induction of cell apoptosis, as convinced by the increase of Sub-G1 peak, PARP cleavage and activation of caspase-3, caspase-7 and caspase-9. Caudatin treatment also resulted in mitochondrial dysfunction which correlated with an imbalance of Bcl-2 family members. Further investigation revealed that caudatin triggered U251 cell apoptosis by inducing reactive oxygen species (ROS) generation through disturbing the redox homeostasis. Moreover, pretreatment of caspase inhibitors apparently weakens caudatin-induced cell killing, PARP cleavage and caspase activation and eventually reverses caudatin-mediated apoptosis. Importantly, caudatin significantly inhibited U251 tumour xenografts in vivo through induction of cell apoptosis involving the inhibition of cell proliferation and angiogenesis, which further validate its value in combating human glioma in vivo. Taken together, the results described above all suggest that caudatin inhibited human glioma cell growth by induction of caspase-dependent apoptosis with involvement of mitochondrial dysfunction and ROS generation.
authors.affiliation: Affiliated Hospital of Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Liang-Zhen
authors.initials: LZ
authors.lastname: Zhu
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Hou
authors.affiliation: Departments of Orthopaedics, Taian Central Hospital, Taian, Shandong, 271000, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Yang
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Fu
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Sun
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Fu
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Lu-Rong
authors.initials: LR
authors.lastname: Shao
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Zhang
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China. tcdfan66@163.com.
authors.forename: Cun-Dong
authors.initials: CD
authors.lastname: Fan
authors.affiliation: School of Pharmacy, Taishan Medical University, Taian, Shandong, 271000, China. ghl007@163.com.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Gao
authors.affiliation: Affiliated Hospital of Taishan Medical University, Taian, Shandong, 271000, China. blsun88@163.com.|Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China. blsun88@163.com.
authors.forename: Bao-Liang
authors.initials: BL
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology*
chemical_list: D061945:Caspase Inhibitors; D006027:Glycosides; D017382:Reactive Oxygen Species; D013256:Steroids; C570806:caudatin; D020169:Caspases
keywords: Apoptosis; Bcl-2 family; Caspase; Caudatin; Glioma; Reactive oxygen species