Reversal Effect of Saikosaponin A and Saikosaponin B on Doxorubicin-resistant Breast Cancer Cells and its Mechanism
Dan Wang1, Duochun Ji1, Danni Wu1, Like Wang1, Chunyan Yu1, Chun Li1, Xiaodong Gai1★★ Corresponding author
- 1College of Basic Medicine, Beihua University, Jilin City, Jilin, China.
CORRESPONDENCE
Xiaodong Gai
College of Basic Medicine, Beihua University, Jilin City, Jilin 132013, China.
Received: 13-11-2022; Accepted: 28-02-2023.
Volume 19, Issue 3 · pp. 700–708 · PUBLISHED 2023 · DOI: 10.1177/09731296231171217
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ABSTRACT
Background: One of the key factors limiting the effectiveness of chemotherapy treatment for malignancies is multidrug resistance (MDR). The MDR phenotype is related to P-glycoprotein (P-gp) expression and function. The main triterpenoid saponins generated from Bupleurum chinense DC (BCDC), saikosaponin A (SSa), has been found to have anti-tumor potential. Saikosaponin B (SSb) has the potential for utility in combination with anticancer drugs as the secondary saikosaponins. Objective: In this study, we looked into the impact of SSa and SSb on doxorubicin (Dox)-resistant breast cancer cells and its underlying mechanisms. Materials and Methods: Dox-resistant breast cancer cells (MCF-7ADR) and MCF-7 cells were used in the study. The experimental cells were divided into a different concentration SSa administration group, a different concentration SSb administration group, and a control group, and the related biochemical parameters of MCF-7 and MCF-7ADR cells were detected. Results: We discovered that SSa and SSb both suppressed MCF-7 and MCF-7ADR cell proliferation in a dose-dependent manner. Additionally, SSa at 2.5 and 5.0 μg/mL and SSb at 3.0 and 7.0 μg/mL could significantly enhance the cytotoxicity of Dox and reverse MDR in MCF-7ADR cells. The combination of Dox and SSa or SSb induced obvious synergistic effects. SSa and SSb could increase the sensitivity of MCF-7ADR cells to Dox by decreasing P-gp expression, increasing intracellular accumulation, and delaying the drug efflux of rhodamine 123 (Rh123, a P-gp substrate). Additionally, SSa and SSb both induced G1-phase arrest in MCF-7ADR cells in the presence of Dox. Conclusion: According to the study, SSa and SSb may be novel MDR reversal medicines for breast cancer chemotherapy and have significant therapeutic significance for MDR during tumor therapy.
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Wang, D., Ji, D., Wu, D., Wang, L., Yu, C., Li, C., & Gai, X. (2023). Reversal Effect of Saikosaponin A and Saikosaponin B on Doxorubicin-resistant Breast Cancer Cells and its Mechanism. Pharmacognosy Magazine, 19(3), 700–708. https://doi.org/10.1177/09731296231171217