PMID- 17854715
OWN - NLM
STAT- MEDLINE
DCOM- 20071220
LR  - 20131121
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 43
IP  - 8
DP  - 2007 Oct 15
TI  - Small interfering RNA-mediated silencing of mitochondrial NADP+-dependent 
      isocitrate dehydrogenase enhances the sensitivity of HeLa cells toward tumor 
      necrosis factor-alpha and anticancer drugs.
PG  - 1197-207
AB  - Tumor necrosis factor-alpha (TNF-alpha) and several anticancer drugs induce the 
      production of reactive oxygen species, which play an important causative role in 
      apoptotic cell death. Recently, we demonstrated that the control of mitochondrial 
      redox balance and the cellular defense against oxidative damage is one of the 
      primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase 
      (IDPm) by supplying NADPH for antioxidant systems. In the present report, we show 
      that silencing of IDPm expression in HeLa cells greatly enhances apoptosis 
      induced by TNF-alpha and anticancer drugs. Transfection of HeLa cells with an 
      IDPm small interfering RNA (siRNA) markedly decreased activity of IDPm, enhancing 
      the susceptibility of anticancer agent-induced apoptosis reflected by 
      morphological evidence of apoptosis, DNA fragmentation, cellular redox status, 
      mitochondria redox status and function, and the modulation of apoptotic marker 
      proteins. These results indicate that IDPm may play an important role in 
      regulating the apoptosis induced by TNF-alpha and anticancer drugs and the 
      sensitizing effect of IDPm siRNA on the apoptotic cell death of HeLa cells offers 
      the possibility of developing a modifier of cancer chemotherapy.
FAU - Kil, In Sup
AU  - Kil IS
AD  - School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook 
      National University, Taegu 702-701, Korea.
FAU - Kim, Sung Youl
AU  - Kim SY
FAU - Lee, Sun Joo
AU  - Lee SJ
FAU - Park, Jeen-Woo
AU  - Park JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070720
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Antineoplastic Agents)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.1.1.41 (Isocitrate Dehydrogenase)
RN  - EC 1.1.1.42 (isocitrate dehydrogenase (NADP+))
RN  - H88EPA0A3N (Staurosporine)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - HeLa Cells
MH  - Humans
MH  - Isocitrate Dehydrogenase/genetics/*metabolism
MH  - Mitochondria/drug effects/enzymology
MH  - RNA, Small Interfering/*physiology
MH  - Staurosporine/*pharmacology
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/pharmacology/*physiology
EDAT- 2007/09/15 09:00
MHDA- 2007/12/21 09:00
CRDT- 2007/09/15 09:00
PHST- 2007/03/28 00:00 [received]
PHST- 2007/07/10 00:00 [revised]
PHST- 2007/07/14 00:00 [accepted]
PHST- 2007/09/15 09:00 [pubmed]
PHST- 2007/12/21 09:00 [medline]
PHST- 2007/09/15 09:00 [entrez]
AID - S0891-5849(07)00490-X [pii]
AID - 10.1016/j.freeradbiomed.2007.07.009 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2007 Oct 15;43(8):1197-207. doi: 
      10.1016/j.freeradbiomed.2007.07.009. Epub 2007 Jul 20.