| Autor: |
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 |
| Rok vydání: |
2011 |
| Předmět: |
|
| Zdroj: |
Basicclinical pharmacologytoxicology. 110(4) |
| ISSN: |
1742-7843 |
| Popis: |
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 40-80 μM 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, SKF96365 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 10-50 μM, 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 40 μM) 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
Plný text