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A Triterpenoid from Thalictrum fortunei Induces Apoptosis in BEL-7402 Cells Through the P53-Induced Apoptosis Pathway
Guangdong Research Institute of Traditional Chinese Medicine, Guangzhou 510520, China
Department of Pharmacy Engineering, Institute of Chemistry and Chemical Engineering, Qiqihar University, Qiqihar 161006, China
School of Pharmacy, South-Central University for Nationalities, Wuhan 430074, China
* Author to whom correspondence should be addressed.
Received: 26 September 2011; in revised form: 4 November 2011 / Accepted: 8 November 2011 / Published: 15 November 2011
Abstract: Thalictrum fortunei S. Moore, a perennial plant distributed in the southeastern part of China, has been used in Traditional Chinese Medicine for thousands of years for its antitumor, antibacterial and immunoregulatory effects. In order to investigate the active components and the mechanism of the anti-tumor effects of Thalictrum fortunei, the growth inhibitory effects of eight triterpenoids isolated from the aerial parts of the plant on tumor cell lines were examined by 3-(4,5)-dimethylthiazoy1-3,5-diphenyltetrazolium bromide (MTT) assay. The MTT-assay results showed that the inhibitory activity of 3-O-β-D-glucopyranosyl-(1→4)-β-D-fucopyranosyl(22S,24Z)-cycloart-24-en-3β,22,26-triol 26-O-β-D-glucopyranoside (1) was stronger than that of the other seven tested triterpenoids on human hepatoma Bel-7402 cell line (Bel-7402), human colon lovo cells (LoVo), human non-small cells lung cancer NCIH-460 cells (NCIH-460) and human gastric carcinoma SGC-7901 cells (SGC-7901) after 48 h treatment in vitro, with the IC50 values of 66.4, 84.8, 73.5, 89.6 μM, respectively. Moreover, the antitumor mechanism of compound 1 on Bel-7402 cell was explored through nucleus dyeing, fluorescence assay, flow cytometry and western blot. The flow cytometric analysis results revealed that compound 1 caused apoptosis and mitochondrial membrane potential (MMP) loss in Bel-7402 cells. A fluorescence assay indicated that intracellular reactive oxygen species (ROS) were markedly provoked by compound 1 treatment compared to control cells. Immunoblot results showed that compound 1 significantly increased the expression levels of cleaved caspase-3, P53 and Bax protein, and decreased the expression level of Bcl-2 protein. These findings indicate that compound 1 inhibits the growth activity of tumor cells, probably through the P53 protein-induced apoptosis pathway.
Keywords: Thalictrum fortunei; anti-tumor; triterpenoid; Bel-7402 cells
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Zhang, X.; Zhao, M.; Chen, L.; Jiao, H.; Liu, H.; Wang, L.; Ma, S. A Triterpenoid from Thalictrum fortunei Induces Apoptosis in BEL-7402 Cells Through the P53-Induced Apoptosis Pathway. Molecules 2011, 16, 9505-9519.
Zhang X, Zhao M, Chen L, Jiao H, Liu H, Wang L, Ma S. A Triterpenoid from Thalictrum fortunei Induces Apoptosis in BEL-7402 Cells Through the P53-Induced Apoptosis Pathway. Molecules. 2011; 16(11):9505-9519.
Zhang, Xiantao; Zhao, Ming; Chen, Lvyi; Jiao, Haoyan; Liu, Hongxia; Wang, Liyan; Ma, Shuwei. 2011. "A Triterpenoid from Thalictrum fortunei Induces Apoptosis in BEL-7402 Cells Through the P53-Induced Apoptosis Pathway." Molecules 16, no. 11: 9505-9519.