Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an 710069, Shaanxi, China.
Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an 710069, Shaanxi, China.
Nutrients. 2020 Jan 18;12(1):246. doi: 10.3390/nu12010246.
Ginsenosides have been reported to possess various pharmacological effects, including anticancer effects. Nevertheless, there are few reports about the antitumor activity and mechanisms of ginsenoside Rg5 against breast cancer cells. In the present study, the major ginsenoside Rb1 was transformed into the rare ginsenoside Rg5 through enzymatic bioconversion and successive acid-assisted high temperature and pressure processing. Ginsenosides Rb1, Rg3, and Rg5 were investigated for their antitumor effects against five human cancer cell lines via the MTT assay. Among them, Rg5 exhibited the greatest cytotoxicity against breast cancer. Moreover, Rg5 remarkably suppressed breast cancer cell proliferation through mitochondria-mediated apoptosis and autophagic cell death. LC3B-GFP/Lysotracker and mRFP-EGFP-LC3B were utilized to show that Rg5 induced autophagosome-lysosome fusion. Western blot assays further illustrated that Rg5 decreased the phosphorylation levels of PI3K, Akt, mTOR, and Bad and suppressed the PI3K/Akt signaling pathway in breast cancer. Moreover, Rg5-induced apoptosis and autophagy could be dramatically strengthened by the PI3K/Akt inhibitor LY294002. Finally, a molecular docking study demonstrated that Rg5 could bind to the active pocket of PI3K. Collectively, our results revealed that Rg5 could be a potential therapeutic agent for breast cancer treatment.
人参皂苷具有多种药理作用，包括抗癌作用。然而，关于人参皂苷 Rg5 对乳腺癌细胞的抗肿瘤活性和机制的报道较少。在本研究中，通过酶法生物转化和连续酸辅助高温高压处理，将主要的人参皂苷 Rb1 转化为罕见的人参皂苷 Rg5。通过 MTT 法测定了人参皂苷 Rb1、Rg3 和 Rg5 对五种人癌细胞系的抗肿瘤作用。其中，Rg5 对乳腺癌的细胞毒性最大。此外，Rg5 通过线粒体介导的细胞凋亡和自噬性细胞死亡显著抑制乳腺癌细胞增殖。LC3B-GFP/Lysotracker 和 mRFP-EGFP-LC3B 用于显示 Rg5 诱导自噬体-溶酶体融合。Western blot 分析进一步表明，Rg5 降低了乳腺癌中 PI3K、Akt、mTOR 和 Bad 的磷酸化水平，并抑制了 PI3K/Akt 信号通路。此外，PI3K/Akt 抑制剂 LY294002 可显著增强 Rg5 诱导的细胞凋亡和自噬。最后，分子对接研究表明，Rg5 可以与人参皂苷 Rg5 结合 PI3K 的活性口袋。总之，我们的研究结果表明，Rg5 可能是治疗乳腺癌的潜在治疗剂。
