Influences of Lovastatin on membrane ion flow and intracellular signalling in breast cancer cells

• Autorzy: Wei N , Mi M.T. , Zhou Y.
• Języki publikacji: EN

Abstrakty

EN

Lovastatin, an inhibitor of cellular cholesterol synthesis, has an apparent anti-cancer property, but the detailed mechanisms of its anti-cancer effects remain poorly understood. We investigated the molecular mechanism of Lovastatin anti-tumor function through the study of its effect on membrane ion flow, gap junctional intercellular communication (GJIC), and the pathways of related signals in MCF-7 mammary cancer cells. After treatment for 24–72 h with 4, 8 or 16 μmol/L Lovastatin, cellular proliferation was examined via the MTT assay, and changes in membrane potential and cellular [Ca2+]i were monitored using confocal laser microscopy. In addition, the expression of plasma membrane calcium ATPase isoform 1 (PMCA1) mRNA was analyzed via RT-PCR, the GJIC function was examined using the scrape-loading dye transfer (SLDT) technique, and MAPK phosphorylation levels were tested with the kinase activity assay. The results showed that Lovastatin treatment significantly inhibited the growth of MCF-7 breast cancer cells. It also increased the negative value of the membrane potential, leading to the hyperpolarization of cells. Moreover, Lovastatin treatment continuously enhanced [Ca2+]i, although the levels of PMCA1 mRNA were unchanged. GJIC was also upregulated in MCF-7 cells, with transfer of LY Fluorescence reaching 4 to 5 rows of cells from the scraped line after treatment with 16 μmol/L Lovastatin for 72 h. Finally, downregulation of ERK1 and p38MAPK phosphorylation were found in Lovastatin-treated MCF-7 cells. It could be deduced that Lovastatin can induce changes in cellular hyperpolarization and intracellular Ca2+ distributions, and increase GJIC function. These effects may result in changes in the downstream signal cascade, inhibiting the growth of MCF-7 cells.

Słowa kluczowe

EN

cellular cholesterol synthesis; cancer cell; Lovastatin; intercellular communication; human breast; antitumour function; cell membrane ion transfer; membrane ion flow; breast cancer

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2007
• Tom: 12
• Numer: 1
• Opis fizyczny: p.1-15,fig.,ref.

Twórcy

autor

Wei N

• Third Military Medical University, Chongqing 400038, P.R.China

autor

Mi M.T.

autor

Zhou Y.

Bibliografia

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