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Artesunate promotes G2/M cell cycle arrest in MCF7 breast cancer cells through ATM activation

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Abstract

Background

Recent studies have revealed that artesunate (ART) has clear anti-tumor activity, suggesting that it could be a good candidate chemotherapeutic agent. In this study, we researched the inhibitory effect of ART on MCF7 cells and explored the possible mechanisms.

Methods

MTT assay was used to detect the effect of ART on the proliferation of MCF7 cells. Crystal violet staining was used to observe morphological and quantitative changes. Flow cytometry was used to detect the cell cycle of the drug-acting MCF7 cells. In addition, western blotting was used to detect the drug influence on expression of the ATM, phospho-ATM(S1981), H2AX, γH2AX(S139), CHK2 and phospho-CHK2(T68), cdc25C, and phospho-cdc25C(S216).

Results

In the experimental groups, the proliferation of MCF7 cells was inhibited in a dose-dependent manner and the original cell morphology was lost. The number of G2/M phase cells in the experimental groups increased significantly, and the expression of DNA damage response-associated proteins was significantly increased, such as phospho-ATM(S1981), γH2AX(S139), phospho-CHK2(T68), and phospho-cdc25C(S216).

Conclusions

ART can inhibit cell proliferation and promote G2/M arrest in MCF7 cells through ATM activation and the ensuing “ATM-Chk2-Cdc25C” pathway, thus implicating ART as a novel candidate for breast cancer chemotherapy.

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Acknowledgements

This work was supported by Natural Science Foundation of Guangdong Province (2014A03031749), Medical Science and Technology Research Foundation of Guangdong Province (A2017359), Shenzhen Science and Technology Project Foundation (JCYJ20150403094227974), and Longgang Science and Technology Project Foundation (YLWS20140610155624914).

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Correspondence to Fengxiang Wei.

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Wen, L., Liu, L., Wen, L. et al. Artesunate promotes G2/M cell cycle arrest in MCF7 breast cancer cells through ATM activation. Breast Cancer 25, 681–686 (2018). https://doi.org/10.1007/s12282-018-0873-5

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  • DOI: https://doi.org/10.1007/s12282-018-0873-5

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