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. 2006 Nov 13;12(1):1–15. doi: 10.2478/s11658-006-0050-2

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

Na Wei 1, Man Tian Mi 1,✉, Yong Zhou 1
PMCID: PMC6275703  PMID: 17103090

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.

Key words: Lovastatin, Human breast cancer cells, Cellular membrane ion transfer, Gap junctional intercellular communication (GJIC), MAPK activity

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Abbreviations used

[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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