PMID- 21701041
OWN - NLM
STAT- MEDLINE
DCOM- 20120313
LR  - 20220410
IS  - 1933-7205 (Electronic)
IS  - 1933-7191 (Linking)
VI  - 18
IP  - 12
DP  - 2011 Dec
TI  - Dichloroacetate induces apoptosis of epithelial ovarian cancer cells through a 
      mechanism involving modulation of oxidative stress.
PG  - 1253-61
LID - 10.1177/1933719111411731 [doi]
AB  - Epithelial ovarian cancer (EOC) cells are under intrinsic oxidative stress, which 
      alters metabolic activity and reduces apoptosis. Key oxidative stress enzymes, 
      including myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS), are 
      upregulated and colocalized in EOC cells. Oxidative stress is also regulated, in 
      part, by superoxide dismutase (SOD) and hypoxia-inducible factor (HIF) 1a. 
      Dichloroacetate (DCA) converts anaerobic to aerobic metabolism and thus was 
      utilized to determine the effects on apoptosis, iNOS, MPO, extracellular SOD 
      (SOD-3), and HIF-1a, in EOC cells. Protein and messenger RNA (mRNA) levels of 
      iNOS, MPO, SOD-3, and HIF-1a were evaluated by immunoprecipitation/Western blot 
      and real-time reverse transcriptase-polymerase chain reaction (RT-PCR), 
      respectively, utilizing SKOV-3 and MDAH-2774 treated with DCA. Apoptosis was 
      assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling 
      (TUNEL) and caspase 3 assays. Dichloroacetate induced apoptosis, reduced MPO, 
      iNOS, and HIF-1a, whereas increased SOD, in both EOC cell lines. In conclusion, 
      reduction of enhanced oxidative stress-induced apoptosis of EOC cells, which may 
      serve as future therapeutic intervention for ovarian cancer.
FAU - Saed, Ghassan M
AU  - Saed GM
AD  - Department of Obstetrics and Gynecology, The CS Mott Center for Human Growth and 
      Development, Wayne State University School of Medicine, Detroit, MI 48201, USA. 
      gsaed@med.wayne.edu
FAU - Fletcher, Nicole M
AU  - Fletcher NM
FAU - Jiang, Zhong L
AU  - Jiang ZL
FAU - Abu-Soud, Husam M
AU  - Abu-Soud HM
FAU - Diamond, Michael P
AU  - Diamond MP
LA  - eng
PT  - Journal Article
DEP - 20110623
PL  - United States
TA  - Reprod Sci
JT  - Reproductive sciences (Thousand Oaks, Calif.)
JID - 101291249
RN  - 0 (Antineoplastic Agents)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (RNA, Messenger)
RN  - 9LSH52S3LQ (Dichloroacetic Acid)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 1.14.13.39 (NOS2 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.15.1.1 (SOD3 protein, human)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Caspase 3/metabolism
MH  - Cell Line, Tumor
MH  - Dichloroacetic Acid/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Epithelial Cells/*drug effects/metabolism/pathology
MH  - Female
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - Immunoprecipitation
MH  - In Situ Nick-End Labeling
MH  - Nitric Oxide Synthase Type II/genetics/metabolism
MH  - Ovarian Neoplasms/genetics/metabolism/*pathology
MH  - Oxidation-Reduction
MH  - Oxidative Stress/*drug effects
MH  - Peroxidase/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Superoxide Dismutase/genetics/metabolism
EDAT- 2011/06/28 06:00
MHDA- 2012/03/14 06:00
CRDT- 2011/06/25 06:00
PHST- 2011/06/25 06:00 [entrez]
PHST- 2011/06/28 06:00 [pubmed]
PHST- 2012/03/14 06:00 [medline]
AID - 1933719111411731 [pii]
AID - 10.1177/1933719111411731 [doi]
PST - ppublish
SO  - Reprod Sci. 2011 Dec;18(12):1253-61. doi: 10.1177/1933719111411731. Epub 2011 Jun 
      23.