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Cytotechnology

, Volume 71, Issue 1, pp 401–409 | Cite as

Thiocoraline mediates drug resistance in MCF-7 cells via PI3K/Akt/BCRP signaling pathway

  • Jin Jin
  • Yujia Zhao
  • Wan Guo
  • Bingrong Wang
  • Yigang Wang
  • Xinyuan Liu
  • Chuanlian XuEmail author
Original Article
  • 30 Downloads

Abstract

Thiocoraline, a depsipeptide bisintercalator with potent antitumor activity, was first isolated from marine actinomycete Micromonospora marina. It possesses an intense toxicity to MCF-7 cells at nanomolar concentrations in a dose-dependent manner evaluated by MTT assay and crystal violet staining. We established a human breast thiocoraline-resistant cancer subline of MCF-7/thiocoraline (MCF-7/T) to investigate the expression variation of breast cancer resistance proteins (BCRP) and its subsequent influence on drug resistance. Colony-forming assay showed that the MCF-7 cells proliferated faster than the MCF-7/T cells in vitro. Western blot analysis demonstrated that thiocoraline increased the phosphorylation of Akt. Additionally, the sensitivity of tumor cells to thiocoraline was reduced with a concurrent rise in phosphorylation level of Akt and of BCRP expression.These studies indicated that thiocoraline probably mediated the drug resistance via PI3K/Akt/BCRP signaling pathway. MK-2206 dihydrochloride, a selective phosphorylation inhibitor of Akt, significantly decreased MCF-7 cell viability under exposure to thiocoraline compared to the control. However, it was not obviously able to decrease MCF-7/T cell viability when cells were exposed to thiocoraline.

Keywords

Thiocoraline MCF-7 Multidrug resistance BCRP PI3K/Akt/BCRP signaling pathway MK-2206 dihydrochloride 

Notes

Acknowledgements

This work was financially supported by Zhejiang academician expert work station service center. Funding Number: 116129A4Q17002. We gratefully acknowledge the support from Dr. Williams Fenical group in Scripps Institution of Oceanography of University of California San Diego for supplying the compound thiocoraline.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Supplementary material

10616_2019_301_MOESM1_ESM.doc (256 kb)
Supplementary material 1 (DOC 255 kb)

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Jin Jin
    • 1
    • 3
  • Yujia Zhao
    • 1
    • 3
  • Wan Guo
    • 1
    • 3
  • Bingrong Wang
    • 1
    • 3
  • Yigang Wang
    • 1
  • Xinyuan Liu
    • 1
    • 2
  • Chuanlian Xu
    • 1
    • 3
    Email author
  1. 1.College of Life SciencesZhejiang Sci-Tech UniversityHangzhouChina
  2. 2.State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina
  3. 3.Xinyuan Institute of Medicine and Biotechnology, College of Life SciencesZhejiang Sci-Tech UniversityHangzhouChina

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