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 |
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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. |
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ISSN: | 0920-9069 1573-0778 |
DOI: | 10.1007/s10616-019-00301-w |