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

Cellular & Molecular Biology Letters volume 12, pages 1–15 (2007)Cite this article

Abstract

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.

Abbreviations

[Ca2+]i :

cytosolic free Ca2+ concentration

GI:

growth inhibition

GJIC:

gap junctional intercellular communication

HMG-CoA:

3-hydroxy-3-methylglutarylcoenzyme A

LOV:

lovastatin

MVA:

mevalonic acid

PMCA1:

plasma membrane calcium ATPase isoform 1

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Authors and Affiliations

  1. Department of Nutrition and Food Hygiene, Third Military Medical University, Chongqing, 400038, P.R. China

    Na Wei, Man Tian Mi & Yong Zhou

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  1. Na Wei
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  2. Man Tian Mi
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Correspondence to Man Tian Mi.

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Wei, N., Mi, M.T. & Zhou, Y. Influences of Lovastatin on membrane ion flow and intracellular signaling in breast cancer cells. Cell Mol Biol Lett 12, 1–15 (2007). https://doi.org/10.2478/s11658-006-0050-2

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Cellular & Molecular Biology Letters

ISSN: 1689-1392

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