Back to Search
Start Over
The mechanism of NPC-14686-induced [Ca²⁺]i rises and non-Ca²⁺-triggered cell death in MG63 human osteosarcoma cells.
- Source :
-
The Chinese journal of physiology [Chin J Physiol] 2014 Jun 30; Vol. 57 (3), pp. 158-66. - Publication Year :
- 2014
-
Abstract
- NPC-14686 has been shown to have anti-inflammatory effect in previous studies, but the mechanisms are unclear. The effect of NPC-14686 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. NPC-14686 at concentrations of 100-500 μM induced a [Ca²⁺]i rise in a concentration-dependent manner. The response was reduced by 80% by removing Ca²⁺. NPC-14686 induced Mn²⁺ influx leading to quenching of fura-2 fluorescence. NPC-14686-evoked Ca²⁺ entry was suppressed by nifedipine, econazole, SK&F96365, and protein kinase C inhibitor. Inhibition of phospholipase C with U73122 abolished NPC-14686-induced [Ca²⁺]i rise. At 20-50 μM, NPC-14686 decreased cell viability, which was not reversed by chelating cytosolic Ca²⁺ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy methyl (BAPTA/AM). Annexin V/propidium iodide staining data suggest that NPC-14686 (30-50 μM) induced apoptosis in a concentration-dependent manner. NPC-14686 also increased levels of reactive oxygen species. Together, in human osteosarcoma cells, NPC-14686 induced a [Ca²⁺]i rise by inducing phospholipase C-dependent Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ entry via protein kinase C-sensitive store-operated Ca²⁺ channels. NPC-14686 induced cell death that might involve apoptosis via mitochondrial pathways.
- Subjects :
- Antifungal Agents pharmacology
Apoptosis physiology
Calcium metabolism
Calcium Channel Blockers pharmacology
Calcium Signaling physiology
Cell Line, Tumor
Cell Survival drug effects
Cell Survival physiology
Chelating Agents pharmacology
Econazole pharmacology
Egtazic Acid analogs & derivatives
Egtazic Acid pharmacology
Humans
Imidazoles pharmacology
Nifedipine pharmacology
Aminobutyrates pharmacology
Apoptosis drug effects
Bone Neoplasms pathology
Calcium Signaling drug effects
Osteosarcoma pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0304-4920
- Volume :
- 57
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Chinese journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 24826784
- Full Text :
- https://doi.org/10.4077/CJP.2014.BAB178