title: Artesunate induces G2/M cell cycle arrest through autophagy induction in breast cancer cells.
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.
authors: aDepartment 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.
authors: Kai
authors: K
authors: Chen
authors: Liu-Mei
authors: LM
authors: Shou
authors: Fang
authors: F
authors: Lin
authors: Wei-Ming
authors: WM
authors: Duan
authors: Meng-Yao
authors: MY
authors: Wu
authors: Xin
authors: X
authors: Xie
authors: Yu-Feng
authors: YF
authors: Xie
authors: Wei
authors: W
authors: Li
authors: Min
authors: M
authors: Tao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D015251:Epirubicin / Q000494:pharmacology; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D037621:Artemisinins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D015251:Epirubicin; D000077332:Artesunate