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

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....

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Veröffentlicht in:Cytotechnology (Dordrecht) 2019-02, Vol.71 (1), p.401-409
Hauptverfasser: Jin, Jin, Zhao, Yujia, Guo, Wan, Wang, Bingrong, Wang, Yigang, Liu, Xinyuan, Xu, Chuanlian
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Sprache:eng
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Zusammenfassung: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.
ISSN:0920-9069
1573-0778
DOI:10.1007/s10616-019-00301-w