The effect of the natural product diindolylmethane on cytosolic Ca2+ concentrations ([Ca2+]i) and viability in PC3 human prostate cancer cells was explored.
The Ca(2+)-sensitive fluorescent dye fura-2 was applied to measure [Ca2+](i). Diindolylmethane at concentrations of 20-50 µM induced [Ca2+]i rise in a concentration-dependent manner. The response was reduced partly by removing Ca2+. Diindolylmethane-evoked Ca2+ entry was suppressed by nifedipine, econazole, SK&F96365, protein kinase C modulators and aristolochic acid. In the absence of extracellular Ca2+, incubation with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited or abolished diindolylmethane-induced [Ca2+]i rise. Incubation with diindolylmethane also inhibited thapsigargin or BHQ-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 reduced diindolylmethane-induced [Ca2+]i rise. At concentrations of 50-100 µM, diindolylmethane killed cells in a concentration-dependent manner. This cytotoxic effect was not altered by chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Annexin V/PI staining data implicate that diindolylmethane (50 and 100 µM) induced apoptosis in a concentration-dependent manner. In conclusion, diindolylmethane induced a [Ca2+]i rise in PC3 cells by evoking phospholipase C-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via phospholipase A2-sensitive store-operated Ca2+ channels. Diindolylmethane caused cell death in which apoptosis may participate.
Written by:
Tsai JY, Chou CT, Liu SI, Liang WZ, Kuo CC, Liao WC, Lin KL, Hsu SS, Lu YC, Huang JK, Jan CR. Are you the author?
Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Reference: J Recept Signal Transduct Res. 2012 Oct;32(5):271-8.
doi: 10.3109/10799893.2012.707212
PubMed Abstract
PMID: 22845469
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