title: The mechanism of carvacrol-evoked [Ca2+]i rises and non-Ca2+-triggered cell death in OC2 human oral cancer cells.
abstract: Carvacrol is one of the main substances of essential oil which triggers intracellular Ca(2+) mobilization and causes cytotoxicity in diverse cell models. However, the mechanism of carvacrol-induced Ca(2+) movement and cytotoxicity is not fully understood. This study examined the effect of carvacrol on cytosolic free Ca(2+) concentrations ([Ca(2+)](i)), cell viability and apoptosis in OC2 human oral cancer cells. Carvacrol induced a [Ca(2+)](i) rise and the signal was reduced by removal of extracellular Ca(2+). Carvacrol-induced Ca(2+) entry was not altered by store-operated Ca(2+) channel inhibitors and protein kinase C (PKC) activator, but was inhibited by a PKC inhibitor. In Ca(2+) -free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) or 2,5-di-tert-butylhydroquinone (BHQ) inhibited carvacrol-induced [Ca(2+)](i) rise. Conversely, incubation with carvacrol inhibited TG or BHQ-induced [Ca(2+)](i) rise. Inhibition of phospholipase C (PLC) with U73122 abolished carvacrol-induced [Ca(2+)](i) rise. Carvacrol decreased cell viability, which was not reversed when cytosolic Ca(2+) was chelated with BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester). Carvacrol-induced apoptosis and activation of reactive oxygen species (ROS) and caspase-3. Together, carvacrol induced a [Ca(2+)](i) rise by inducing PLC-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via PKC-sensitive, non store-operated Ca(2+) channels. Carvacrol-induced ROS- and caspase-3-associated apoptosis.
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, ROC.
authors.forename: Wei-Zhe
authors.initials: WZ
authors.lastname: Liang
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
authors.forename: Ti
authors.initials: T
authors.lastname: Lu
authors.forename: Chao-Chuan
authors.initials: CC
authors.lastname: Chi
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Tseng
authors.forename: Chih-Chuan
authors.initials: CC
authors.lastname: Pan
authors.forename: Ko-Long
authors.initials: KL
authors.lastname: Lin
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Kuo
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000081007:Cymenes; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008297:Male; D039821:Monoterpenes / Q000494:pharmacology*; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D000081007:Cymenes; D039821:Monoterpenes; D017382:Reactive Oxygen Species; C073316:carvacrol; D011493:Protein Kinase C; D010738:Type C Phospholipases; D053148:Caspase 3; D002118:Calcium