Ginsenoside Rh1 Induces MCF-7 Cell Apoptosis and Autophagic Cell Death through ROS-Mediated Akt Signaling

• Published in: Cancers Vol. 13; no. 8; p. 1892
• Main Authors: Huynh, Diem Thi Ngoc, Jin, Yujin, Myung, Chang-Seon, Heo, Kyung-Sun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15-04-2021; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Antitumor activity; Apoptosis; Autophagy; Breast cancer; Cancer; Cancer therapies; Caspase-3; Cell cycle; Cell death; Cell growth; Chemotherapy; Cytotoxicity; Enzyme inhibitors; Flow cytometry; Ginsenosides; Immunofluorescence; Immunohistochemistry; Kinases; Multidrug resistance; Phagocytosis; Phosphorylation; Propidium iodide; Reactive oxygen species; Retina; Retinoblastoma; Signal transduction; Sulforhodamine; Western blotting; Xenografts; apoptosis; autophagy; Akt; ginsenoside Rh1; reactive oxygen species
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers13081892

Breast cancer (BC) is the leading cause of cancer-related deaths among women worldwide. Ginsenosides exhibit anticancer activity against various cancer cells. However, the effects of ginsenoside Rh1 on BC and the underlying mechanisms remain unknown. Here, we investigated the anticancer effects of Rh1 on human BC MCF-7 and HCC1428 cells and the underlying signaling pathways. The anticancer effects of Rh1 in vitro were evaluated using sulforhodamine B (SRB), 3-(4, 5-dimethylthiazole-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), clonogenic assay, propidium iodide (PI)/Hoechst staining, Western blotting, flow cytometry, and immunofluorescence analysis. The in vivo effects of Rh1 were determined using a xenograft model via hematoxylin and eosin and the immunohistochemistry staining of tumor tissues. We found that Rh1 exerted cytotoxicity in the cells by increasing cell apoptosis, autophagy, and cell cycle arrest. These effects were further enhanced by a phosphatidylinositol 3-kinase (PI3K) inhibitor but were rescued by the inhibition of reactive oxygen species (ROS). Moreover, enhanced ROS generation by Rh1 inhibited the activation of the PI3K/Akt pathway. Consistently, Rh1 treatment significantly reduced tumor growth in vivo and increased the ROS production and protein expression of LC3B and cleaved caspase-3 but decreased the phosphorylation of Akt and retinoblastoma (Rb) in tumor tissues. Taken together, Rh1 exerted a potential anticancer effect on BC cells by inducing cell cycle arrest, apoptosis, and autophagy via inhibition of the ROS-mediated PI3K/Akt pathway.