Effect of [6]-shogaol on cytosolic Ca2+ levels and proliferation in human oral cancer cells (OC2).
The effect of [6]-shogaol (1) on cytosolic free Ca(2+) concentrations ([Ca(2+)](i)) and viability has not been explored previously in oral epithelial cells. The present study has examined whether 1 alters [Ca(2+)](i) and viability in OC2 human oral cancer cells. Compound 1 at concentrations > or = 5 microM increased [Ca(2+)](i) in a concentration-dependent manner with a 50% effective concentration (EC(50)) value of 65 microM. The Ca(2+) signal was reduced substantially by removing extracellular Ca(2+). In a Ca(2+)-free medium, the 1-induced [Ca(2+)](i) elevation was mostly attenuated by depleting stored Ca(2+) with thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). The [Ca(2+)](i) signal was inhibited by La(3+) but not by L-type Ca(2+) channel blockers. The elevation of [Ca(2+)](i) caused by 1 in a Ca(2+)-containing medium was not affected by modulation of protein kinase C activity, but was inhibited by 82% with the phospholipase A2 inhibitor aristolochic acid I (20 microM). U73122, a selective inhibitor of phospholipase C, abolished 1-induced [Ca(2+)](i) release. At concentrations of 5-100 microM, 1 killed cells in a concentration-dependent manner. These findings suggest that [6]-shogaol induces a significant rise in [Ca(2+)](i) in oral cancer OC2 cells by causing stored Ca(2+) release from the thapsigargin-sensitive endoplasmic reticulum pool in an inositol 1,4,5-trisphosphate-dependent manner and by inducing Ca(2+) influx via a phospholipase A2- and La(3+)-sensitive pathway.
Chen
Chung-Yi
CY
Department of Medical Technology, School of Medical and Health Sciences, Fooyin University, Ta-liao, Kaohsiung County 83101, Taiwan, Republic of China.
Yang
Yu-Han
YH
Kuo
Soong-Yu
SY
D002118:Calcium / Q000032:analysis*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D015394:Molecular Structure; D009062:Mouth Neoplasms; D064801:Phospholipase A2 Inhibitors; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D020746:Calcium Channels, L-Type; D002396:Catechols; D004963:Estrenes; D064801:Phospholipase A2 Inhibitors; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D019284:Thapsigargin; C040115:shogaol; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D002118:Calcium