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Matrine Activates PTEN to Induce Growth Inhibition and Apoptosis in V600EBRAF Harboring Melanoma Cells
School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
Yue-yang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
East Hospital, Tongji University, Shanghai 200120, China
* Author to whom correspondence should be addressed.
Received: 17 May 2013; in revised form: 12 July 2013 / Accepted: 18 July 2013 / Published: 31 July 2013
Abstract: Here, we report a natural chemical Matrine, which exhibits anti-melanoma potential with its PTEN activation mechanism. Matrine effectively inhibited proliferation of several carcinoma cell lines, including melanoma V600EBRAF harboring M21 cells. Flow cytometry analysis showed Matrine induced G0/G1 cell cycle arrest in M21 cells dose-dependently. Apoptosis in M21 cells induced by Matrine was identified by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis and Annexin-V/FITC staining. Molecular mechanistic study suggested that Matrine upregulated both mRNA level and protein expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN), leading to inhibition of the PI3K/Akt pathway. Downregulation of phosphor-Aktser473 by Matrine activated p21 and Bax, which contributed to G0/G1 cell cycle and apoptosis. Besides, Matrine enhanced the PI3K/Akt inhibition effects to inhibit the cell proliferation with PI3K inhibitor, LY2940002. In summary, our findings suggest Matrine is a promising antitumor drug candidate with its possible PTEN activation mechanisms for treating cancer diseases, such as melanomas.
Keywords: Matrine; cell cycle arrest; apoptosis; V600EBRAF melanoma; PTEN
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MDPI and ACS Style
Jin, H.; Sun, Y.; Wang, S.; Cheng, X. Matrine Activates PTEN to Induce Growth Inhibition and Apoptosis in V600EBRAF Harboring Melanoma Cells. Int. J. Mol. Sci. 2013, 14, 16040-16057.
Jin H, Sun Y, Wang S, Cheng X. Matrine Activates PTEN to Induce Growth Inhibition and Apoptosis in V600EBRAF Harboring Melanoma Cells. International Journal of Molecular Sciences. 2013; 14(8):16040-16057.
Jin, Hui; Sun, Yu; Wang, Shuiying; Cheng, Xiaodong. 2013. "Matrine Activates PTEN to Induce Growth Inhibition and Apoptosis in V600EBRAF Harboring Melanoma Cells." Int. J. Mol. Sci. 14, no. 8: 16040-16057.