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

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

  • Mol Cell Biochem. 2022 Nov 21. doi: 10.1007/s11010-022-04597-9.
Fang Hua # 1 2,  Yi-Yi Xiao # 2,  Xin-Hui Qu 1 3,  Shan-Shan Li 1 4,  Kun Zhang 1,  Chao Zhou 1 3,  Jian-Le He 1 3,  Ye Zhu 1 3,  Yu-Ying Wan 5,  Li-Ping Jiang 2,  Fang-Fang Tou 6 7,  Xiao-Jian Han 8 9
Affiliations

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.
  • 2 Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
  • 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.
  • 4 Department of Internal Medicine, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
  • 5 Department of Intra-Hospital Infection Management, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
  • 6 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. toufangfang@163.com.
  • 7 Department of Oncology, Jiangxi Provincial People's Hospital &, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, People's Republic of China. toufangfang@163.com.
  • 8 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. hanxiaojian@hotmail.com.
  • 9 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. hanxiaojian@hotmail.com.
  • # Contributed equally.
PMID: 36413334 DOI: 10.1007/s11010-022-04597-9
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.

Keywords

Autophagy; Baicalein; Cyclin-dependent kinase 1; Doxorubicin; Triple negative breast cancer.

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