Abstract
Simple SummaryBreast cancer (BC) is the most common cause of cancer-related deaths among women worldwide, and its incidence has been increasing. However, current therapeutic approaches, such as chemotherapy, radiation, and hormonal therapy, have become increasingly ineffective because of their severe adverse effects and multidrug resistance. Therefore, the discovery of new potential candidates for BC therapy is essential. Here, we investigated whether ginsenoside Rh1 exhibits anticancer effects on BC. We found that this ginsenoside effectively inhibited the growth of BC cells in both cell cultures and mice. Therefore, ginsenoside Rh1 is a promising candidate for BC treatment.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.
Highlights
IntroductionCancer is a major global health issue that has been increasing dramatically
Involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in the antitumor effect of Rh1 in MCF-7 cells was confirmed using a PI3K inhibitor, LY294002 (5 μM), and we found that LY294002 further decreased the phosphorylation of Akt and mTOR compared to the treatment with
Akt phosphorylation in the tumors of Rh1-treated mice was dose-dependently decreased, as shown by immunofluorescence staining (Figure 7F, two lower panels, and Figure 7G). These results indicate that Rh1 possesses potential antitumor properties in breast cancer (BC) in vivo and further confirmed the in vitro results, in which Rh1 induced autophagy, apoptosis, and cell cycle arrest through
Summary
Cancer is a major global health issue that has been increasing dramatically. Among the different types of cancer, breast cancer (BC) is commonly associated with cancer-related deaths in women [1]. Chemotherapy, radiation, hormonal therapy, and surgery have been used as therapies for BC. Because of severe adverse effects and multidrug resistance, these therapeutic approaches have become increasingly ineffective [2]. Discovering new potential candidates for BC therapy is essential, and natural compounds have been attracting great attention owing to their promising anticancer properties [3]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
