2. Academic Validation
  3. 20(S)-Protopanaxadiol-Induced Apoptosis in MCF-7 Breast Cancer Cell Line through the Inhibition of PI3K/AKT/mTOR Signaling Pathway

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 Apr 2;19(4):1053. doi: 10.3390/ijms19041053.
Hong Zhang 1 2 3,  Hua-Li Xu 4,  Yu-Chen Wang 5,  Ze-Yuan Lu 6,  Xiao-Feng Yu 7,  Da-Yun Sui 8
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China. zlzhoan@163.com.
  • 2 School of Materials Science and Engineering, South China University of Technology, Guangzhou 510640, China. zlzhoan@163.com.
  • 3 R&D Center, Guangzhou Ribobio Co., Ltd., Guangzhou 510663, China. zlzhoan@163.com.
  • 4 Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China. xhl@jlu.edu.cn.
  • 5 Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China. scarwyc@163.com.
  • 6 Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China. zeyuanlu@jlu.edu.cn.
  • 7 Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China. xiaofengyu1962@163.com.
  • 8 Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China. suidy@jlu.edu.cn.
PMID: 29614812 DOI: 10.3390/ijms19041053
Abstract

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.

Keywords

20(S)-Protopanaxadiol; MCF-7; PI3K/AKT/mTOR; apoptosis.

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