3,3'-Diindolylmethane Alters Ca 2+ Homeostasis and Viability in MG63 Human Osteosarcoma Cells

Yi Chau Lu, I. Shu Chen, Chiang Ting Chou, Jong Khing Huang, Hong Tai Chang, Jeng Yu Tsai, Shu Shong Hsu, Wei Chuan Liao, Jue Long Wang, Ko Long Lin, Shuih Inn Liu, Chun Chi Kuo, Chin Man Ho, Chung Ren Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

12 Scopus citations

Abstract

The effect of the natural product 3,3'-diindolylmethane (DIM) on cytosolic Ca 2+ concentrations ([Ca 2+] i) and viability in MG63 human osteosarcoma cells was explored. The Ca 2+-sensitive fluorescent dye fura-2 was applied to measure [Ca 2+] i. DIM at concentrations of 40-80μM induced a [Ca 2+] i rise in a concentration-dependent manner. The response was reduced partly by removing Ca 2+. DIM-evoked Ca 2+ entry was suppressed by nifedipine, econazole, SK&F96365 and protein kinase C modulators. In the absence of extracellular Ca 2+, incubation with the endoplasmic reticulum Ca 2+ pump inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited or abolished DIM-induced [Ca 2+] i rise. Incubation with DIM also inhibited thapsigargin or BHQ-induced [Ca 2+] i rise. Inhibition of phospholipase C with U73122 abolished DIM-induced [Ca 2+] i rise. At concentrations of 10-50μM, DIM killed cells in a concentration-dependent manner. This cytotoxic effect was not altered by chelating cytosolic Ca 2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Annexin V/propidium iodide staining data implicate that DIM (20 and 40μM) induced apoptosis in a concentration-dependent manner. In sum, in MG63 cells, DIM induced a [Ca 2+] i rise by evoking phospholipase C-dependent Ca 2+ release from the endoplasmic reticulum and Ca 2+ entry via protein kinase C-sensitive store-operated Ca 2+ channels. DIM caused cell death that may involve apoptosis.

Original languageEnglish
Pages (from-to)314-321
Number of pages8
JournalBasic and Clinical Pharmacology and Toxicology
Volume110
Issue number4
DOIs
StatePublished - 04 2012
Externally publishedYes

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