PMID- 23146755
OWN - NLM
STAT- MEDLINE
DCOM- 20130307
LR  - 20191210
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 303
DP  - 2013 Jan 7
TI  - The mechanism of carvacrol-evoked [Ca2+]i rises and non-Ca2+-triggered cell death 
      in OC2 human oral cancer cells.
PG  - 152-61
LID - S0300-483X(12)00382-4 [pii]
LID - 10.1016/j.tox.2012.10.026 [doi]
AB  - 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.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Liang, Wei-Zhe
AU  - Liang WZ
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung 813, Taiwan, ROC.
FAU - Chou, Chiang-Ting
AU  - Chou CT
FAU - Lu, Ti
AU  - Lu T
FAU - Chi, Chao-Chuan
AU  - Chi CC
FAU - Tseng, Li-Ling
AU  - Tseng LL
FAU - Pan, Chih-Chuan
AU  - Pan CC
FAU - Lin, Ko-Long
AU  - Lin KL
FAU - Kuo, Chun-Chi
AU  - Kuo CC
FAU - Jan, Chung-Ren
AU  - Jan CR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121109
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Calcium Channels)
RN  - 0 (Cymenes)
RN  - 0 (Monoterpenes)
RN  - 0 (Reactive Oxygen Species)
RN  - 9B1J4V995Q (carvacrol)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - EC 3.4.22.- (Caspase 3)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Calcium/*metabolism
MH  - Calcium Channels/metabolism
MH  - Carcinoma, Squamous Cell/*drug therapy/pathology
MH  - Caspase 3/metabolism
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cymenes
MH  - Cytosol/metabolism
MH  - Endoplasmic Reticulum/metabolism
MH  - Humans
MH  - Male
MH  - Monoterpenes/*pharmacology
MH  - Mouth Neoplasms/*drug therapy/pathology
MH  - Protein Kinase C/drug effects/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Type C Phospholipases/metabolism
EDAT- 2012/11/14 06:00
MHDA- 2013/03/08 06:00
CRDT- 2012/11/14 06:00
PHST- 2012/09/26 00:00 [received]
PHST- 2012/10/31 00:00 [accepted]
PHST- 2012/11/14 06:00 [entrez]
PHST- 2012/11/14 06:00 [pubmed]
PHST- 2013/03/08 06:00 [medline]
AID - S0300-483X(12)00382-4 [pii]
AID - 10.1016/j.tox.2012.10.026 [doi]
PST - ppublish
SO  - Toxicology. 2013 Jan 7;303:152-61. doi: 10.1016/j.tox.2012.10.026. Epub 2012 Nov 
      9.