Astilbotriterpenic Acid Induces Growth Arrest and Apoptosis in HeLa Cells through Mitochondria-Related Pathways and Reactive Oxygen Species (ROS) Production

作者：Zhang Yi Bin; Ye Yi Ping; Wu Xiao Dan; Sun Hong Xiang^*

来源：Chemistry and Biodiversity, 2009, 6(2): 218-230.

DOI：10.1002/cbdv.200700427

Astilbotriterpenic acid (1), 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 (Ay)m) with the alterations of Bcl-2/Bar 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.

• 出版日期2009
• 单位浙江省医学科学院; 浙江大学