期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 749, 期 -, 页码 20-31出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2014.12.021
关键词
Prostate cancer; Sodium butyrate; T-type calcium channel; Neuroendooine differentiation
资金
- UMES School of Pharmacy
- U.S. Department of Education [P031B090209]
- National Institute of General Medical Sciences [T34GM008411]
Several cellular mechanisms contribute to the neuroenclocrine differentiation of prostate cancer cells, including exposure to sodium butyrate (NaBu), a naturally occurring salt of the short chain fatty acid n-butyric acid. NaBu belongs to a class of histone deacetylase inhibitors with potential anticancer function. T-type calcium channel expression constitutes an important route for calcium influx in tumor cells that may trigger changes in cell proliferation and differentiation. In this work we investigated the role NaBu on the differentiation of lymph node carcinoma of the prostate (LNCaP) cells and its effect on T-type Ca2+-channel expression. NaBu stimulates the morphological and molecular differentiation of LNCaP cells. Stimulation of LNCaP cells with NaBu evokes a significant increase in the expression of the Ca(v)3.2 T-type channel subunits. Furthermore, the increased Ca(v)3.2 expression promotes membrane insertion of T-type Ca2+ channels capable of generating fast inactivating Ca2+ currents, sensitive to 100 mu M Ni2+ ions. Inhibition of T-type Ca2+ channel function reduces the outgrowth of neurite-like processes in LNCaP cells. NaBu-evoked expression of T-type Ca2+ channels is also involved in the regulation of cell viability. Inhibition of T-type Ca2+ channels causes a significant reduction in the viability of LNCaP cells treated with 1 mM NaBci, suggesting that Ca2+ influx via T-type channels can promote cell proliferation. However, increased expression of T-type Ca2+ channels enhanced the cytotoxic effect of thapsigargin and paclitaxel on cell proliferation. These findings demonstrate that NaBu stimulates T-type Ca2+ channel expression, thereby regulating both the morphological differentiation and growth of prostate cancer cells. (C) 2015 Elsevier B.V. All rights reserved.
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