PMID- 16413115
OWN - NLM
STAT- MEDLINE
DCOM- 20070125
LR  - 20181201
IS  - 0304-3835 (Print)
IS  - 0304-3835 (Linking)
VI  - 244
IP  - 1
DP  - 2006 Nov 28
TI  - 9-cis-Retinoic acid inhibition of lung carcinogenesis in the A/J mouse model is 
      accompanied by increased expression of RAR-beta but no change in 
      cyclooxygenase-2.
PG  - 101-8
AB  - 9-cis-Retinoic acid (9cRA) binds both retinoic acid receptors (RARs) and retinoid 
      X receptors (RXRs) and has been shown to be a potential chemopreventive agent 
      both in lung cancer cell culture studies and in clinical trials studying former 
      smokers. However, direct evidence of the efficacy of 9cRA against lung tumor 
      development in vivo is lacking. In the present study, we determined whether 
      treatment with 9cRA has the potential to inhibit lung carcinogenesis by 
      upregulating RAR-beta and down-regulating COX-2 expression in the A/J mouse lung 
      cancer model. A/J mice (n=14-15/group) were treated as follows: (1) Control (Sham 
      treated); (2) NNK (100mg NNK/kg body weight); (3) NNK+9cRA (15mg/kg diet); and 
      (4) NNK+celecoxib (a COX-2-specific inhibitor, 500mg/kg diet). Tumor incidence, 
      tumor multiplicity, RAR-beta mRNA, COX-2 mRNA, and COX-2 protein levels in lung 
      samples of mice were determined 4 months after carcinogen injection. The results 
      showed that mice receiving 9cRA supplementation had significantly lower tumor 
      multiplicity (48% reduction, P<0.05) and showed a trend toward lower tumor 
      incidence (40% reduction, P=0.078), as compared with the mice given NNK alone. 
      Although, celecoxib treatment resulted in greater declines in tumor incidence and 
      tumor multiplicity (75 and 88%, respectively, P<0.05), the chemoprotective 
      effects of celecoxib were accompanied by increased mortality while 9cRA treatment 
      resulted in no weight-loss associated toxicity or mortality. Supplementation with 
      9cRA was effective in increasing RAR-beta mRNA, but this increase was not 
      accompanied by decreased levels of COX-2 mRNA or protein. These results suggest 
      that 9cRA supplementation may provide protection against lung carcinogenesis and 
      this effect may be mediated in part by 9cRA induction of RAR-beta, but not 
      inhibition of COX-2 transcription.
FAU - Mernitz, Heather
AU  - Mernitz H
AD  - Nutrition and Cancer Biology Laboratory, Jean Mayer United States Department of 
      Agriculture Human Nutrition Research Center on Aging at Tufts University, 711 
      Washington Street, Boston, MA 02111, USA.
FAU - Smith, Donald E
AU  - Smith DE
FAU - Zhu, Andrew X
AU  - Zhu AX
FAU - Wang, Xiang-Dong
AU  - Wang XD
LA  - eng
GR  - R01CA104932/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20060118
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Carcinogens)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nitrosamines)
RN  - 0 (Pyrazoles)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Sulfonamides)
RN  - 0 (retinoic acid receptor beta)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
RN  - 7S395EDO61 (4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - JCX84Q7J1L (Celecoxib)
SB  - IM
MH  - Alitretinoin
MH  - Animals
MH  - Antineoplastic Agents/*therapeutic use
MH  - Carcinogens/toxicity
MH  - Celecoxib
MH  - Cell Transformation, Neoplastic/*drug effects
MH  - Cyclooxygenase 2/*metabolism
MH  - Cyclooxygenase 2 Inhibitors/pharmacology
MH  - Dietary Supplements
MH  - *Disease Models, Animal
MH  - Lung/drug effects
MH  - Lung Neoplasms/chemically induced/metabolism/*prevention & control
MH  - Male
MH  - Membrane Proteins/antagonists & inhibitors/*metabolism
MH  - Mice
MH  - Mice, Inbred A
MH  - Nitrosamines/toxicity
MH  - Pyrazoles/pharmacology
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Sulfonamides/pharmacology
MH  - Tretinoin/*therapeutic use
EDAT- 2006/01/18 09:00
MHDA- 2007/01/26 09:00
CRDT- 2006/01/18 09:00
PHST- 2005/08/24 00:00 [received]
PHST- 2005/12/04 00:00 [accepted]
PHST- 2006/01/18 09:00 [pubmed]
PHST- 2007/01/26 09:00 [medline]
PHST- 2006/01/18 09:00 [entrez]
AID - S0304-3835(05)01048-7 [pii]
AID - 10.1016/j.canlet.2005.12.001 [doi]
PST - ppublish
SO  - Cancer Lett. 2006 Nov 28;244(1):101-8. doi: 10.1016/j.canlet.2005.12.001. Epub 
      2006 Jan 18.