Astilbotriterpenic acid induces growth arrest and apoptosis in HeLa cells through mitochondria-related pathways and reactive oxygen species (ROS) production.
Astilbotriterpenic acid, a novel ursane-type triterpenoid from the rhizomes of Astilbe chinensis, has cytostatic properties in several cancer cell lines and induces apoptosis in HeLa cell. The aim of this study was to investigate the mechanisms by which such properties are exerted, with special reference to the anti-proliferative and apoptotic potential on HeLa cells. Compound 1 showed a marked concentration- and time-dependent inhibition of HeLa cell proliferation, and induced G(0)/G(1) phase arrest of HeLa cell in a dose-dependent manner. There was a quick attenuation of mitochondrial membrane potential (Deltapsi(m)) with the alterations of Bcl-2/Bax mRNA express value in 1-treated HeLa, indicating the participation of a mitochondria-related mechanism. Pretreatment of a pan-caspase inhibitor (benzyloxycarbonyl)-Val-Ala-Asp-(fluoromethyl) ketone (z-VAD-fmk) significantly increases the viability of 1-treated HeLa cells implied that the participation of caspase; Western-blot analysis showed the activation of initiator caspase-8 and caspase-9, and executor caspase-3. Meanwhile, treatment with 1 stimulates the generation of reactive oxygen species (ROS) in HeLa cell. Taken together, our data showed that compound 1 induced growth arrest and apoptosis in HeLa cells through mitochondria-related pathways and ROS production, and may be further evaluated as a chemotherapeutic agent for human cancer.
Zhang
Yi-Bin
YB
College of Animal Sciences, Zhejiang University, Hangzhou 310029, P. R. China.
Ye
Yi-Ping
YP
Wu
Xiao-Dan
XD
Sun
Hong-Xiang
HX
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D016193:G1 Phase; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
C527656:3,6-dihydroxyurs-12-en-27-oic acid; D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014315:Triterpenes; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D020169:Caspases