PMID- 18473858
OWN - NLM
STAT- MEDLINE
DCOM- 20080623
LR  - 20190728
IS  - 1873-4286 (Electronic)
IS  - 1381-6128 (Linking)
VI  - 14
IP  - 11
DP  - 2008
TI  - Chemosensitization of cancer by nitric oxide.
PG  - 1113-23
AB  - Recent evidence from experimental and clinical studies links the development of 
      intratumoral hypoxia and oxidative stress with malignant progression. Cellular 
      adaptation induced by these environmental stresses is also associated with the 
      emergence of drug resistant populations. This adaptation is most likely a 
      multifactorial process involving coordination of various stress-induced signaling 
      pathways, including those regulated by hypoxia-inducible factor-1 (HIF-1) and 
      nuclear factor kappaB (NF-kappaB) together with their downstream targets linked 
      to resistance mechanisms. Experimental data suggest that treatment of human 
      cancer cells with nitric oxide (NO) and NO mimetic agents can effectively restore 
      the sensitivity of resistant populations to the cytotoxic effects of 
      chemotherapeutics both in vitro and in vivo. Furthermore, preliminary results 
      from Phase II clinical trials evaluating NO as an adjuvant to chemotherapy are 
      promising. The present review highlights the significance of intratumoral hypoxia 
      and oxidative stress in the emergence of multidrug resistance, and summarizes the 
      latest data demonstrating the chemosensitizing ability of NO. To date, the 
      specific mechanisms through which NO restores sensitivity to anticancer agents 
      are not clearly understood. However, the data suggest that chemosensitization is 
      likely to involve NO-mediated activities associated with both prevention and 
      inhibition of cellular drug resistance mechanisms. Potential mechanisms 
      contributing to the chemosensitizing activity of NO include vascular changes that 
      promote increased blood delivery and tumor oxygenation, antioxidant effects and 
      down-regulation of the glutathione detoxification/redox buffering system, 
      inhibition of key transcription factors such as HIF-1 and NF-kappaB, as well as 
      inhibition of drug efflux transporters and DNA repair enzymes.
FAU - Sullivan, Richard
AU  - Sullivan R
AD  - Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, 
      Canada K7L 3N6.
FAU - Graham, Charles H
AU  - Graham CH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United Arab Emirates
TA  - Curr Pharm Des
JT  - Current pharmaceutical design
JID - 9602487
RN  - 0 (Antineoplastic Agents)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Clinical Trials as Topic
MH  - Drug Resistance, Neoplasm
MH  - Humans
MH  - Neoplasms/*drug therapy/pathology
MH  - Nitric Oxide/*pharmacology
MH  - Oxidative Stress/drug effects
MH  - Signal Transduction
RF  - 124
EDAT- 2008/05/14 09:00
MHDA- 2008/06/24 09:00
CRDT- 2008/05/14 09:00
PHST- 2008/05/14 09:00 [pubmed]
PHST- 2008/06/24 09:00 [medline]
PHST- 2008/05/14 09:00 [entrez]
AID - 10.2174/138161208784246225 [doi]
PST - ppublish
SO  - Curr Pharm Des. 2008;14(11):1113-23. doi: 10.2174/138161208784246225.