9-cis-Retinoic acid inhibition of lung carcinogenesis in the A/J mouse model is accompanied by increased expression of RAR-β but no change in cyclooxygenase-2

Mernitz, Heather; Smith, Donald E.; Wang, Xiangdong

doi:10.1016/j.canlet.2005.12.001

Cited by 20 publications

(23 citation statements)

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“…13 In this study, treatment with 9cRA at doses of 7.5 and 15 mg/kg diet was shown to effectively decrease lung tumor multiplicity without appreciable weight loss, confirming earlier findings from our lab. 14 The ability of 9cRA to alter tumor multiplicity suggests that this treatment is acting to inhibit tumorigenesis at an early stage in the process of tumor promotion. This observation complements existing literature documenting the chemopreventive effects of high-dose retinoids in the prevention of new primary tumors in patients curatively resected for stage I lung cancer.…”

Section: Discussionmentioning

confidence: 99%

“…41,42 Previous studies, including ours, have shown that a single intraperitoneal injection of 2 mg or 100 mg/kg body weight of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific carcinogen, is sufficient to induce tumors in 100% of A/J mice at a level of 10-12 lung adenomas per mouse at 16 weeks post-injection. 14,43 Male A/J mice (6 weeks old) obtained from Jackson Labs (Bar Harbor, ME) were randomly assigned to 1 of 9 experimental groups (n 5 14/group). Each group was fed an AIN-93M powdered semipurified diet (Dyets, Bethlehem, PA) for 14 days, and then begun on study diets as described below:…”

Section: Animal Model and Experimental Designmentioning

confidence: 99%

“…13 We have recently shown that treatment with 9cRA (15 mg/kg diet) induced RARb expression and decreased lung tumor multiplicity in the A/J mouse model of lung cancer. 14 Epidemiological and ecological studies have shown correlations between low sunlight exposure or low serum vitamin D and an increased risk of cancer, suggesting a role for vitamin D in the prevention of many types of cancer. [15][16][17] Further, target genes regulated by vitamin D and its deltanoid analogs have been identified using oligonucleotide microarrays and include genes that control inter-and intracellular signaling, cell adhesion, extracellular matrix composition, cell cycle progression and immune system function.…”

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Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Mernitz

Smith

Wood

et al. 2007

Intl Journal of Cancer

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9-cis-Retinoic acid (9cRA) and 1a, 25-dihydroxyvitamin D 3 (1,25D) show promise as potential chemopreventive agents. We examined 9cRA and 1,25D, alone and in combination, for their potential to inhibit carcinogen (NNK)-induced lung carcinogenesis in A/J mice. A/J mice (n 5 14/group) were treated with 9cRA (7.5, 15, or 30 mg/kg diet), 1,25D (2.5 or 5.0 lg/kg diet), or a combination of 9cRA (15 mg/kg diet) plus 1,25D (2.5 lg/kg diet) for 3 weeks before and 17 weeks after carcinogen injection. Lung tumor incidence, tumor multiplicity, plasma 1,25D levels and kidney expression of vitamin D 24-hydroxylase (CYP24) were determined. Compared to carcinogen-injected controls, mice receiving 9cRA supplementation had significantly lower tumor multiplicity at all doses (decreased 68-85%), with body weight loss at the higher doses of 9cRA. Mice receiving 1,25D supplementation had significantly lower tumor incidence (decreased 36 and 82%) and tumor multiplicity (decreased 85 and 98%), but experienced significant body weight loss, kidney calcium deposition, elevated kidney CYP24 expression and decreased fasting plasma 1,25D levels. Although, there was no apparent influence on chemopreventive efficacy, addition of 9cRA to 1,25D treatment effectively prevented the weight loss and kidney calcification associated with 1,25D treatment alone. These data demonstrate that 9cRA and 1,25D, alone or combined, can inhibit lung tumor promotion in the A/J mouse model. Combining 1,25D with 9cRA has the potential to mitigate the toxicity of 1,25D, while preserving the significant effect of 1,25D treatment against lung carcinogenesis. The underlying mechanism behind this effect does not appear to be related to retinoid modulation of vitamin D catabolism. ' 2006 Wiley-Liss, Inc.Key words: lung cancer; 9-cis retinoic acid; 1a,25-dihydroxyvitamin D 3Chemoprevention by diet or drug intervention may offer a realistic and practical means of modifying the risk of lung cancer, the leading cause of cancer deaths in both men and women in the United States. 1 Two classes of chemopreventive compounds that have been considered are the retinoids and the active form of vitamin D, 1a,25-dihydroxyvitamin D 3 (1,25D, also calcitriol).Retinoids are required for proper differentiation of lung and upper airway epithelium, 2 and both 9-cis retinoic acid (9cRA, also 9-cis tretinoin) and all-trans retinoic acid have been shown to inhibit cell growth and proliferation in lung cancer cell lines. 3 Studies in animal models of lung cancer suggest that retinoids may be effective in cancer chemoprevention in vivo, but results have varied with species, dose and timing of treatment in relation to induction of carcinogenesis. [4][5][6] In human lung cancer, epidemiological evidence supports a role for vitamin A-rich foods and supplements in protection against the development of lung cancer in smokers and nonsmokers alike 7 ; however, clinical trials assessing the efficacy of retinoid supplementation against lung cancer have yielded inconsistent and inconclusive results. [8][...

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Section: Discussionmentioning

confidence: 99%

Section: Animal Model and Experimental Designmentioning

confidence: 99%

mentioning

confidence: 99%

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Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Mernitz

Smith

Wood

et al. 2007

Intl Journal of Cancer

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“…Some antioxidants (β-carotene, α-tocopherol, and ascorbic acid) have been demonstrated 4-Ipomeanol analogs A/J mice Inhibiting NNK metabolism [142] to effectively prevent NNK-induced lung carcinogenesis in smoke-exposed ferrets through restoring retinoic acid to the normal level and inhibiting the JNK and MAPK pathways [132]. Moreover, β-cryptoxanthin [117] and 9-cis-retinoic acid [116] were also found to exhibit anti-tumor activities via restoration of the nicotine-inhibited expression of lung SIRT1, p53, and RARβ. These results imply that RARβ signaling pathway may be a potential target for lung cancer treatments.…”

Section: Chemopreventive Agents Against Nnk-induced Lung Cancermentioning

confidence: 99%

Tobacco carcinogen NNK-induced lung cancer animal models and associated carcinogenic mechanisms

Ge¹,

Xu²,

Chen³

2015

ABBS

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Tobacco usage is a major risk factor in the development, progression, and outcomes for lung cancer. Of the carcinogens associated with lung cancer, tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is among the most potent ones. The oncogenic mechanisms of NNK are not entirely understood, hindering the development of effective strategies for preventing and treating smoking-associated lung cancers. Here, we introduce the NNK-induced lung cancer animal models in different species and its potential mechanisms. Finally, we summarize several chemopreventive agents developed from these animal models.

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“…In addition, the level of COX-2 has been reported to negatively correlate with retinoic acid receptor beta (RARβ) [13][14][15], the level of which has been proved to strongly connect to retinoid sensitivity [4]. However, a study conducted by Mernitz failed to confirm this correlation [16]. We conducted this study to determine the combined effects of celecoxib and all-trans retinoic acid (ATRA)…”

Section: Introductionmentioning

confidence: 99%

Celecoxib increases retinoid sensitivity in human colon cancer cell lines

Liu

Zheng

et al. 2010

Cellular and Molecular Biology Letters

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Abstract:Retinoid resistance has limited the clinical application of retinoids as differentiation-inducing and apoptosis-inducing drugs. This study was designed to investigate whether celecoxib, a selective COX-2 inhibitor, has effects on retinoid sensitivity in human colon cancer cell lines, and to determine the possible mechanism of said effects. Cell viability was measured using the MTT assay. Apoptosis was detected via Annexin-V/PI staining and the flow cytometry assay. PGE 2 production was measured with the ELISA assay. The expression of RARβ was assayed via western blotting. The results showed that celecoxib enhanced the inhibitory effect of ATRA in both COX-2 high-expressing HT-29 and COX-2 low-expressing SW480 cell lines. Further study showed the ATRA and celecoxib combination induced greater apoptosis, but that the addition of PGE 2 did not affect the enhanced growth-inhibitory and apoptosis-inducing effects of the combination. Moreover, NS398 (another selective COX-2 inhibitor) did not affect the inhibitory effects of ATRA in the two cell lines. Western blotting showed that the expression of RARβ in HT-29 cell lines was increased by celecoxib, but not by NS398, and that the addition of PGE 2 did not affect the celecoxib-induced expression of the retinoic acid receptor beta. In conclusion, celecoxib increased the expression of RARβ and the level of cellular ATRA sensitivity through COX-2-independent mechanisms. This finding may provide a potential strategy for combination therapy.

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9-cis-Retinoic acid inhibition of lung carcinogenesis in the A/J mouse model is accompanied by increased expression of RAR-β but no change in cyclooxygenase-2

Cited by 20 publications

References 45 publications

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Tobacco carcinogen NNK-induced lung cancer animal models and associated carcinogenic mechanisms

Celecoxib increases retinoid sensitivity in human colon cancer cell lines

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9-cis-Retinoic acid inhibition of lung carcinogenesis in the A/J mouse model is accompanied by increased expression of RAR-β but no change in cyclooxygenase-2

Cited by 20 publications

References 45 publications

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D3 and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D3 and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Tobacco carcinogen NNK-induced lung cancer animal models and associated carcinogenic mechanisms

Celecoxib increases retinoid sensitivity in human colon cancer cell lines

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Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity