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Open AccessArticle

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

1
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
2
Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou 350000, China
3
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Alan C. Leonard
Int. J. Mol. Sci. 2015, 16(8), 19401-19418; https://doi.org/10.3390/ijms160819401
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)
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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MDPI and ACS Style

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. https://doi.org/10.3390/ijms160819401

AMA Style

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. International Journal of Molecular Sciences. 2015; 16(8):19401-19418. https://doi.org/10.3390/ijms160819401

Chicago/Turabian Style

Lan, Qiusheng; Li, Shoufeng; Lai, Wei; Xu, Heyang; Zhang, Yang; Zeng, Yujie; Lan, Wenjian; Chu, Zhonghua. 2015. "Methyl Sartortuoate Inhibits Colon Cancer Cell Growth by Inducing Apoptosis and G2/M-Phase Arrest" Int. J. Mol. Sci. 16, no. 8: 19401-19418. https://doi.org/10.3390/ijms160819401

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