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- Title
3,3′-Diindolylmethane Alters Ca<sup>2+</sup> Homeostasis and Viability in MG63 Human Osteosarcoma Cells.
- Authors
Lu, Yi-Chau; Chen, I-Shu; Chou, Chiang-Ting; Huang, Jong-Khing; Chang, Hong-Tai; Tsai, Jeng-Yu; Hsu, Shu-Shong; Liao, Wei-Chuan; Wang, Jue-Long; Lin, Ko-Long; Liu, Shuih-Inn; Kuo, Chun-Chi; Ho, Chin-Man; Jan, Chung-Ren
- Abstract
The effect of the natural product 3,3′-diindolylmethane (DIM) on cytosolic Ca2+ concentrations ([Ca2+]i) and viability in MG63 human osteosarcoma cells was explored. The Ca2+-sensitive fluorescent dye fura-2 was applied to measure [Ca2+]i. DIM at concentrations of 40-80 μM induced a [Ca2+]i rise in a concentration-dependent manner. The response was reduced partly by removing Ca2+. DIM-evoked Ca2+ entry was suppressed by nifedipine, econazole, SK&F96365 and protein kinase C modulators. In the absence of extracellular Ca2+, incubation with the endoplasmic reticulum Ca2+ pump inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited or abolished DIM-induced [Ca2+]i rise. Incubation with DIM also inhibited thapsigargin or BHQ-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 abolished DIM-induced [Ca2+]i rise. At concentrations of 10-50 μM, DIM 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/propidium iodide staining data implicate that DIM (20 and 40 μM) induced apoptosis in a concentration-dependent manner. In sum, in MG63 cells, DIM induced a [Ca2+]i rise by evoking phospholipase C-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via protein kinase C-sensitive store-operated Ca2+ channels. DIM caused cell death that may involve apoptosis.
- Subjects
BRASSICACEAE; OSTEOSARCOMA; PROTEIN kinase inhibitors; CANCER cell growth; FURA-2
- Publication
Basic & Clinical Pharmacology & Toxicology, 2012, Vol 110, Issue 4, p314
- ISSN
1742-7835
- Publication type
Article
- DOI
10.1111/j.1742-7843.2011.00816.x