title: Regulation of T-type calcium channel expression by sodium butyrate in prostate cancer cells.
abstract: Several cellular mechanisms contribute to the neuroendocrine 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 Ca(2+) 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 Cav3.2 T-type channel subunits. Furthermore, the increased Cav3.2 expression promotes membrane insertion of T-type Ca(2+) channels capable of generating fast inactivating Ca(2+) currents, sensitive to 100μM Ni(2+) ions. Inhibition of T-type Ca(2+) channel function reduces the outgrowth of neurite-like processes in LNCaP cells. NaBu-evoked expression of T-type Ca(2+) channels is also involved in the regulation of cell viability. Inhibition of T-type Ca(2+) channels causes a significant reduction in the viability of LNCaP cells treated with 1mM NaBu, suggesting that Ca(2+) influx via T-type channels can promote cell proliferation. However, increased expression of T-type Ca(2+) channels enhanced the cytotoxic effect of thapsigargin and paclitaxel on cell proliferation. These findings demonstrate that NaBu stimulates T-type Ca(2+) channel expression, thereby regulating both the morphological differentiation and growth of prostate cancer cells.
authors.affiliation: Department of Natural Sciences, School of Agricultural and Natural Sciences, University of Maryland Eastern Shore, Princess Anne, MD 21853, USA.
authors.forename: Erika M
authors.initials: EM
authors.lastname: Weaver
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, MD 21853, USA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Zamora
authors.affiliation: Department of Natural Sciences, School of Agricultural and Natural Sciences, University of Maryland Eastern Shore, Princess Anne, MD 21853, USA.
authors.forename: Yvonne A
authors.initials: YA
authors.lastname: Puplampu-Dove
authors.affiliation: Department of Natural Sciences, School of Agricultural and Natural Sciences, University of Maryland Eastern Shore, Princess Anne, MD 21853, USA.
authors.forename: Ezechielle
authors.initials: E
authors.lastname: Kiessu
authors.affiliation: Department of Natural Sciences, School of Agricultural and Natural Sciences, University of Maryland Eastern Shore, Princess Anne, MD 21853, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hearne
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, MD 21853, USA. Electronic address: mmartin@umes.edu.
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin-Caraballo
mesh_terms: D020148:Butyric Acid / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D017239:Paclitaxel / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: C479952:CACNA1H protein, human; D020747:Calcium Channels, T-Type; D056572:Histone Deacetylase Inhibitors; D020148:Butyric Acid; D019284:Thapsigargin; D017239:Paclitaxel
keywords: 5-Azacytidine (PubChem CID: 9444); NNC 55-0396 (PubChem CID: 11957578); Neuroendocrine differentiation; Paclitaxel (PubChem CID: 36314); Prostate cancer; Sodium butyrate; Sodium butyrate (PubChem CID: 5222465); Suberoylanilide hydroxamic acid (PubChem CID: 5311); T-type calcium channel; Thapsigargin (PubChem CID: 446378)