PMID- 12160937
OWN - NLM
STAT- MEDLINE
DCOM- 20030203
LR  - 20190826
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 33
IP  - 4
DP  - 2002 Aug 15
TI  - Intracellular glutathione is a cofactor in methylseleninic acid-induced apoptotic 
      cell death of human hepatoma HEPG(2) cells.
PG  - 552-61
AB  - Selenium is a widely studied dietary anticancer agent. Among various selenium 
      compounds, the methylated forms appear to be particularly effective in cancer 
      prevention. Intracellular glutathione (GSH) is known to be involved in the 
      metabolism of many methylated forms of selenium. In this study, we investigated 
      the role of intracellular GSH in methylseleninic acid (MSeA)-induced apoptosis in 
      human hepatoma (HepG(2)) cells. MSeA was shown to deplete intracellular GSH 
      rapidly, preceding the typical apoptotic changes such as DNA fragmentation as 
      measured by the TUNEL assay. When the intracellular GSH concentration was 
      enhanced using N-acetylcysteiene (NAC) (a GSH synthesis precursor) and decreased 
      using buthionine sufoxamine (BSO) (a GSH synthesis inhibitor), NAC markedly 
      augmented MSeA-induced apoptosis, while BSO significantly inhibited MSeA-induced 
      apoptosis. Different from the effect of sodium selenite, there was no measurable 
      superoxide radical level in MSeA-treated cells. These observations suggest that 
      intracellular GSH mainly acts as a cofactor to facilitate MSeA-induced apoptosis, 
      while its antioxidant function becomes largely irrelevant. It is thus postulated 
      that some cancer cells, such as liver cancer cells with higher level of 
      intracellular GSH, would be more susceptible to MSeA cytotoxicity.
FAU - Shen, Han-Ming
AU  - Shen HM
AD  - Department of Community, Occupational, and Family Medicine, National University 
      of Singapore, Republic of Singapore. cofshm@nus.edu.sg
FAU - Ding, Wen-Xing
AU  - Ding WX
FAU - Ong, Choon-Nam
AU  - Ong CN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Organoselenium Compounds)
RN  - 0 (Reactive Oxygen Species)
RN  - 9900C6V162 (methylselenic acid)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Anticarcinogenic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Carcinoma, Hepatocellular/*pathology
MH  - Glutathione/*physiology
MH  - Humans
MH  - Intracellular Membranes/drug effects/physiology
MH  - Liver Neoplasms/*pathology
MH  - Luminescent Measurements
MH  - Membrane Potentials/drug effects
MH  - Mitochondria, Liver/drug effects
MH  - Models, Biological
MH  - Organoselenium Compounds/*pharmacology
MH  - Oxidation-Reduction
MH  - Oxidative Stress
MH  - Reactive Oxygen Species/metabolism
MH  - Tumor Cells, Cultured/drug effects/pathology
EDAT- 2002/08/06 10:00
MHDA- 2003/02/04 04:00
CRDT- 2002/08/06 10:00
PHST- 2002/08/06 10:00 [pubmed]
PHST- 2003/02/04 04:00 [medline]
PHST- 2002/08/06 10:00 [entrez]
AID - S0891584902009188 [pii]
AID - 10.1016/s0891-5849(02)00918-8 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2002 Aug 15;33(4):552-61. doi: 
      10.1016/s0891-5849(02)00918-8.