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Published on: May 14, 2016
Artesunate induces G2/M cell cycle arrest through autophagy induction in breast cancer cells
Kai Chen1, Liu-Mei Shou, Fang Lin
1aDepartment of Oncology, the First Affiliated Hospital of Soochow University bDepartment of Pharmacology and Laboratory of Aging and Nervous Diseases, Soochow University School of Pharmaceutical Science cJiangsu Institute of Clinical Immunology, Suzhou, China.
Abstract:
We found that artesunate (ART) inhibited the growth of MCF-7 and MDA-MB-231 breast cancer cells. ART arrested the cell cycle in the G2/M phase, which was accompanied by an upregulation of p21. ART upregulated the expression of Beclin1, an initiator of autophagy (type II programmed cell death). In addition, ART stimulated the aggregation of LC3, which is considered to be a marker of autophagosome formation. We further verified the transformation of LC3 from type I into type II. 3-MA, a classical autophagy inhibitor, attenuated ART-induced autophagosome formation, cell growth repression, G2/M arrest, and p21 upregulation. Autophagy induction and p21 upregulation were also repressed by knockdown of Beclin1. Furthermore, ART sensitized breast cancer cells to the chemotherapeutic agent epirubicin through an autophagy-dependent cascade. Our study showed that ART induced autophagy in breast cancer cells and indicated that the anticancer effects of ART were exerted through an autophagy pathway. Moreover, ART sensitized breast cancer cells to epirubicin chemotherapy. Our results provide a basis for further development of ART as a novel therapeutic agent for the treatment of breast cancer.
Insights
Artesunate (ART) inhibits breast cancer cell growth by inducing autophagy, a type of cell death. ART also enhances chemotherapy effectiveness, suggesting its potential as a novel breast cancer treatment.
Area of Science:
- Molecular Biology
- Cancer Research
- Pharmacology
Background:
- Breast cancer remains a significant global health challenge.
- Novel therapeutic strategies are urgently needed to improve treatment outcomes.
- Artesunate (ART), an antimalarial drug, shows potential anticancer properties.
Purpose of the Study:
- To investigate the mechanism of action of artesunate (ART) in breast cancer cells.
- To determine the role of autophagy in ART-induced anticancer effects.
- To evaluate ART's potential to sensitize breast cancer cells to chemotherapy.
Main Methods:
- Cell viability assays were performed on MCF-7 and MDA-MB-231 breast cancer cell lines.
- Cell cycle analysis and Western blotting were used to assess cell cycle arrest and protein expression (p21, Beclin1, LC3).
- Autophagy was modulated using 3-methyladenine (3-MA) and Beclin1 knockdown.
- Synergistic effects of ART and epirubicin were evaluated.
Main Results:
- Artesunate inhibited breast cancer cell proliferation and induced G2/M cell cycle arrest.
- ART upregulated p21 expression and induced autophagy, evidenced by increased Beclin1 and LC3-II formation.
- Inhibition of autophagy (using 3-MA or Beclin1 knockdown) reversed ART-induced effects.
- ART sensitized breast cancer cells to epirubicin chemotherapy via an autophagy-dependent pathway.
Conclusions:
- Artesunate exerts anticancer effects in breast cancer cells by inducing autophagy and cell cycle arrest.
- Autophagy plays a crucial role in mediating the anti-breast cancer activity of ART.
- ART enhances the efficacy of epirubicin chemotherapy, highlighting its potential as a novel therapeutic agent for breast cancer treatment.
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