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Int. J. Mol. Sci. 2015, 16(8), 19401-19418;

Methyl Sartortuoate Inhibits Colon Cancer Cell Growth by Inducing Apoptosis and G2/M-Phase Arrest

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou 350000, China
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editor: Alan C. Leonard
Received: 9 June 2015 / Revised: 29 July 2015 / Accepted: 30 July 2015 / Published: 17 August 2015
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
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The potential anti-neoplastic activity of terpenoids is of continued interest. In this study, we investigate whether methyl sartortuoate, a terpenoid isolated from soft coral, induced cell cycle arrest and apoptosis in a human colon cancer cell line. Culture studies found that methyl sartortuoate inhibited colon cancer cell (LoVo and RKO) growth and caused apoptotic death in a concentration- and time-dependent manner, by activation of caspase-8, caspase-9, caspase-3, p53 and Bax, and inactivation of B-cell lymphoma 2 (Bcl-2) apoptosis regulating proteins. Methyl sartortuoate treatment led to reduced expression of cdc2 and up-regulated p21 and p53, suggesting that Methyl sartortuoate induced G2-M arrest through modulation of p53/p21/cdc2 pathways. Methyl sartortuoate also up-regulated phospho-JNK and phospho-p38 expression levels. This resulted in cell cycle arrest at the G2-M phase and apoptosis in LoVo and RKO cells. Treatment with the JNK inhibitor SP600125 and the p38 MAPK inhibitor SB203580 prevented methyl sartortuoate-induced apoptosis in LoVo cells. Moreover, methyl sartortuoate also prevented neoplasm growth in NOD-SCID nude mice inoculated with LoVo cells. Taken together, these findings suggest that methyl sartortuoate is capable of leading to activation of caspase-8, -9, -3, increasing p53 and Bax/Bcl-2 ratio apoptosis through MAPK-dependent apoptosis and results in G2-M phase arrest in LoVo and RKO cells. Thus, methyl sartortuoate may be a promising anticancer candidate. View Full-Text
Keywords: methyl sartortuoate; colon cancer; apoptosis; G2-M arrest; MAPK methyl sartortuoate; colon cancer; apoptosis; G2-M arrest; MAPK

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Lan, Q.; Li, S.; Lai, W.; Xu, H.; Zhang, Y.; Zeng, Y.; Lan, W.; Chu, Z. Methyl Sartortuoate Inhibits Colon Cancer Cell Growth by Inducing Apoptosis and G2/M-Phase Arrest. Int. J. Mol. Sci. 2015, 16, 19401-19418.

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