1. 3,3′-Diindolylmethane Alters Ca2+ Homeostasis and Viability in MG63 Human Osteosarcoma Cells.
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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, and Jan, Chung-Ren
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BRASSICACEAE ,OSTEOSARCOMA ,PROTEIN kinase inhibitors ,CANCER cell growth ,FURA-2 - Abstract
The effect of the natural product 3,3′-diindolylmethane (DIM) on cytosolic Ca
2+ 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. [ABSTRACT FROM AUTHOR]- Published
- 2012
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