title: Effect of thymol on Ca2+ homeostasis and viability in human glioblastoma cells.
abstract: The effect of the natural essential oil thymol on cytosolic Ca(2+) concentrations ([Ca(2+)](i)) and viability in human glioblastoma cells was examined. The Ca(2+)-sensitive fluorescent dye fura-2 was applied to measure [Ca(2+)](i). Thymol at concentrations of 400-1000 μM induced a [Ca(2+)](i) rise in a concentration-dependent fashion. The response was decreased partially by removal of extracellular Ca(2+). Thymol-induced Ca(2+) signal was not altered by nifedipine, econazole, SK&F96365, and protein kinase C activator phorbol myristate acetate (PMA), but was inhibited by the protein kinase C inhibitor GF109203X. When extracellular Ca(2+) was removed, incubation with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) abolished thymol-induced [Ca(2+)](i) rise. Incubation with thymol also abolished thapsigargin or BHQ-induced [Ca(2+)](i) rise. Inhibition of phospholipase C with U73122 abolished thymol-induced [Ca(2+)](i) rise. At concentrations of 200-800 μM, thymol killed cells in a concentration-dependent manner. This cytotoxic effect was not changed by chelating cytosolic Ca(2+) 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 thymol (200, 400 and 600 μM) induced apoptosis in a concentration-dependent manner. Collectively, in human glioblastoma cells, thymol induced a [Ca(2+)](i) rise by inducing phospholipase C- and protein kinase C-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via non store-operated Ca(2+) channels. Thymol induced cell death that may involve apoptosis.
authors.affiliation: Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
authors.forename: Shu-Shong
authors.initials: SS
authors.lastname: Hsu
authors.forename: Ko-Long
authors.initials: KL
authors.lastname: Lin
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
authors.forename: An-Jen
authors.initials: AJ
authors.lastname: Chiang
authors.forename: Wei-Zhe
authors.initials: WZ
authors.lastname: Liang
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Chang
authors.forename: Jeng-Yu
authors.initials: JY
authors.lastname: Tsai
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Liao
authors.forename: Fong-Dee
authors.initials: FD
authors.lastname: Huang
authors.forename: Jong Khing
authors.initials: JK
authors.lastname: Huang
authors.forename: I-Shu
authors.initials: IS
authors.lastname: Chen
authors.forename: Shuih-Inn
authors.initials: SI
authors.lastname: Liu
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; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016257:Fura-2 / Q000378:metabolism; D005909:Glioblastoma / Q000473:pathology*; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D008345:Manganese / Q000378:metabolism; D013943:Thymol / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D013943:Thymol; D008345:Manganese; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2