Thiocoraline mediates drug resistance in MCF-7 cells via PI3K/Akt/BCRP signaling pathway
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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.
KeywordsThiocoraline MCF-7 Multidrug resistance BCRP PI3K/Akt/BCRP signaling pathway MK-2206 dihydrochloride
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.
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Conflict of interest
The authors declare that they have no conflict of interests.
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