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Baicalein sensitizes triple negative breast cancer MDA-MB-231 cells to doxorubicin via autophagy-mediated down-regulation of CDK1

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Abstract

Triple negative breast cancer (TNBC) is a kind of refractory cancer with poor response to conventional chemotherapy. Recently, the combination of baicalein and doxorubicin was reported to exert a synergistic antitumor effect on breast cancer. However, the underlying mechanism how baicalein sensitizes breast cancer cells to doxorubicin remains to be elucidated. Here, it was found that 20 μM baicalein increased the autophagy markers including the ratio of LC3B II/I, GFP-LC3 punctate aggregates and down-regulation of p62 expression, and up-regulated mitophagy marker PINK1 and Parkin in TNBC MDA-MB-231 cells as well. In contrast, doxorubicin decreased the levels of autophagy markers, and significantly up-regulated CDK1 in MDA-MB-231 cells. Pretreatment with baicalein markedly inhibited the doxorubicin-induced decrease in autophagy markers and up-regulation of CDK1, which was reversed by the autophagy inhibitor 3-Methyladenine. Moreover, baicalein alleviated the doxorubicin-induced expression and phosphorylation (at Ser616) of mitochondrial fission protein Drp1. Intriguingly, the autophagy inhibitor 3-Methyladenine also significantly weakened the effect of baicalein on doxorubicin-induced viability decrease and apoptosis in MDA-MB-231 cells. Taken together, our data indicate that baicalein improves the chemosensitivity of TNBC cells to doxorubicin through promoting the autophagy-mediated down-regulation of CDK1, also suggest a novel strategy for prevention of TNBC in the future.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by National Natural Science Foundation of China (81472371), Jiangxi Province Major discipline and academic leaders training Program Project (20172BCB22028), the Research Fund for Jiangxi Geriatric Clinical Medical Research Center (2020BCG74003), Key Research and Development Program of Jiangxi Province (20192BBG70049), Science and Technology Plan Projects of Administration of Traditional Chinese Medicine of Jiangxi Province (2022B063) and the Innovation Fund Designated for Graduate Students of Jiangxi Province (YC2019-S014).

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Author notes

  1. Fang Hua and Yi-Yi Xiao have contributed equally to this work.

Authors and Affiliations

  1. Institute of Geriatrics, Jiangxi Provincial People’s Hospital &, The First Affiliated Hospital of Nanchang Medical College, 152 Aiguo Road, Nanchang, Jiangxi, 330006, People’s Republic of China

    Fang Hua, Xin-Hui Qu, Shan-Shan Li, Kun Zhang, Chao Zhou, Jian-Le He, Ye Zhu, Fang-Fang Tou & Xiao-Jian Han

  2. Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China

    Fang Hua, Yi-Yi Xiao & Li-Ping Jiang

  3. The Second Department of Neurology, Jiangxi Provincial People’s Hospital &, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, People’s Republic of China

    Xin-Hui Qu, Chao Zhou, Jian-Le He, Ye Zhu & Xiao-Jian Han

  4. Department of Internal Medicine, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China

    Shan-Shan Li

  5. Department of Intra-Hospital Infection Management, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China

    Yu-Ying Wan

  6. Department of Oncology, Jiangxi Provincial People’s Hospital &, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, People’s Republic of China

    Fang-Fang Tou

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  1. Fang Hua
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Contributions

All authors contributed to this study. The experiments were conceived and designed by XJH and FFT. The cellular and molecular biological experiments were conducted by FH, YYX, XHQ, SSL and KZ. The flow cytometry was performed by SSL, CZ and JLH. Data collection and analysis were performed by YZ, LPJ and YYW. The first draft of the manuscript was written by XJH and FFT, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Fang-Fang Tou or Xiao-Jian Han.

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We would like to declare on behalf of my co-authors that the work was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. The manuscript is approved by all authors for publication.

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Hua, F., Xiao, YY., Qu, XH. et al. Baicalein sensitizes triple negative breast cancer MDA-MB-231 cells to doxorubicin via autophagy-mediated down-regulation of CDK1. Mol Cell Biochem 478, 1519–1531 (2023). https://doi.org/10.1007/s11010-022-04597-9

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