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Open AccessArticle

20(S)-Protopanaxadiol-Induced Apoptosis in MCF-7 Breast Cancer Cell Line through the Inhibition of PI3K/AKT/mTOR Signaling Pathway

by 1,2,3,†, 1,†, 1, 1, 1,* and 1,*
1
Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China
2
School of Materials Science and Engineering, South China University of Technology, Guangzhou 510640, China
3
R&D Center, Guangzhou Ribobio Co., Ltd., Guangzhou 510663, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(4), 1053; https://doi.org/10.3390/ijms19041053
Received: 2 March 2018 / Revised: 17 March 2018 / Accepted: 27 March 2018 / Published: 2 April 2018
20(S)-Protopanaxadiol (PPD) is one of the major active metabolites of ginseng. It has been reported that 20(S)-PPD shows a broad spectrum of antitumor effects. Our research study aims were to investigate whether apoptosis of human breast cancer MCF-7 cells could be induced by 20(S)-PPD by targeting the Phosphatidylinositol 3-kinase/Protein kinase B/Mammalian target of rapamycin (PI3K/AKT/mTOR) signal pathway in vitro and in vivo. Cell cycle analysis was performed by Propidium Iodide (PI) staining. To overexpress and knock down the expression of mTOR, pcDNA3.1-mTOR and mTOR small interfering RNA (siRNA) transient transfection assays were used, respectively. Cell viability and apoptosis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-test and Annexin V /PI double-staining after transfection. The antitumor effect in vivo was determined by the nude mice xenograft assay. After 24 h of incubation, treatment with 20(S)-PPD could upregulate phosphorylated-Phosphatase and tensin homologue deleted on chromosome 10 (p-PTEN) expression and downregulate PI3K/AKT/mTOR-pathway protein expression. Moreover, G0/G1 cell cycle arrest in MCF-7 cells could be induced by 20(S)-PPD treatment at high concentrations. Furthermore, overexpression or knockdown of mTOR could inhibit or promote the apoptotic effects of 20(S)-PPD. In addition, tumor volumes were partially reduced by 20(S)-PPD at 100 mg/kg in a MCF-7 xenograft model. Immunohistochemical staining indicated a close relationship between the inhibition of tumor growth and the PI3K/AKT/mTOR signal pathway. PI3K/AKT/mTOR pathway-mediated apoptosis may be one of the potential mechanisms of 20(S)-PPD treatment. View Full-Text
Keywords: 20(S)-Protopanaxadiol; PI3K/AKT/mTOR; MCF-7; apoptosis 20(S)-Protopanaxadiol; PI3K/AKT/mTOR; MCF-7; apoptosis
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Zhang, H.; Xu, H.-L.; Wang, Y.-C.; Lu, Z.-Y.; Yu, X.-F.; Sui, D.-Y. 20(S)-Protopanaxadiol-Induced Apoptosis in MCF-7 Breast Cancer Cell Line through the Inhibition of PI3K/AKT/mTOR Signaling Pathway. Int. J. Mol. Sci. 2018, 19, 1053.

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