Retinoic acid and retinoid receptors: potential chemopreventive and therapeutic role in cervical cancer

Abu, Jafaru; Batuwangala, Madu; Herbert, Karl E.; Symonds, Paul

doi:10.1016/s1470-2045(05)70319-3

Cited by 81 publications

(58 citation statements)

References 65 publications

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“…The induced differentiation of tumor cells is regarded to be therapeutically advantageous, since more extensively differentiated neuroblastic tumors are usually associated with lower stage and better clinical outcome. Therefore, differentiating agents such as retinoic acid, which is known to induce differentiation in several tumor types including neuroblastoma, have become a part of the therapeutic arsenal (10)(11)(12)20,32).…”

Section: Discussionmentioning

confidence: 99%

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Influence of LOX/COX inhibitors on cell differentiation induced by all-trans retinoic acid in neuroblastoma cell lines

Rédová

Chlapek²,

Loja³

et al. 2009

Int J Mol Med

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Abstract.We investigated the possible modulation by LOX/ COX inhibitors of all-trans retinoic acid (ATRA)-induced cell differentiation in two established neuroblastoma cell lines, SH-SY5Y and SK-N-BE(2). Caffeic acid, as an inhibitor of 5-lipoxygenase, and celecoxib, as an inhibitor of cyclooxygenase-2, were chosen for this study. The effects of the combined treatment with ATRA and LOX/COX inhibitors on neuroblastoma cells were studied using cell morphology assessment, detection of differentiation markers by immunoblotting, measurement of proliferation activity, and cell cycle analysis and apoptosis detection by flow cytometry. The results clearly demonstrated the potential of caffeic acid to enhance ATRA-induced cell differentiation, especially in the SK-N-BE(2) cell line, whereas application of celecoxib alone or with ATRA led predominantly to cytotoxic effects in both cell lines. Moreover, the higher sensitivity of the SK-N-BE(2) cell line to combined treatment with ATRA and LOX/COX inhibitors suggests that cancer stem cells are a main target for this therapeutic approach. Nevertheless, further detailed study of the phenomenon of enhanced cell differentiation by expression profiling is needed.

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Section: Discussionmentioning

confidence: 99%

“…Induced differentiation of transformed cells into mature phenotypes represents a promising strategy in recent antitumor therapy (10)(11)(12)(13). Among various inductors of differentiation, retinoids are the most frequently investigated.…”

Section: Introductionmentioning

confidence: 99%

Influence of LOX/COX inhibitors on cell differentiation induced by all-trans retinoic acid in neuroblastoma cell lines

Rédová

Chlapek²,

Loja³

et al. 2009

Int J Mol Med

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“…When at-RA is used therapeutically in the treatment of various cancers, plasma clearance is increased contributing to tolerance [45]. Since at-RA has been used for the treatment of acute promyelotic leukemia [40,41] and uterine cervical cancer [3,39,46], nonlethal mutations might counteract tolerance. Therefore, CYP26A1 could make a contribution to hepatic metabolism of this compound in individuals treated with retinoids.…”

Section: Discussionmentioning

confidence: 99%

“…The identification of genetic variants of human CYP26A1 which affect at-RA metabolism will particularly useful in clinical studies of various developmental disorders. at-RA has been used for the treatment of acute promyelotic leukemia [40,41] and uterine cervical cancer [3,39,46], nonlethal mutations might affect blood levels of retinoids. Western blot analysis of the expression of CYP26A1 wild-type and CYP26A1 variants in COS-1 cells.…”

Section: Discussionmentioning

confidence: 99%

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The discovery of new coding alleles of human CYP26A1 that are potentially defective in the metabolism of all-trans retinoic acid and their assessment in a recombinant cDNA expression system

Lee¹,

Perera²,

Coulter³

et al. 2007

Pharmacogenetics and Genomics

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Retinoic acid (RA) is a critical regulator of gene expression during embryonic development and in the maintenance of adult epithelial tissues. Genetic polymorphisms of CYP26A1 could cause interindividual variation in the metabolism of retinoic acid, thus altering signaling during embryonic development. A total of 13 single nucleotide polymorphisms (SNPs) were identified in CYP26A1 in 92 racially diverse individuals (24 Caucasians, 24 African-Americans, 24 Asians and 20 individuals of unknown racial origin). Three of the 13 SNPS produced coding changes: R173S, F186L and C358R. These alleles were termed CYP26A1*2, CYP26A1*3, and CYP26A1*4, respectively, by the Human Cytochrome P450 (CYP) Allele Nomenclature Committee at http://www.cypalleles.ki.se/. cDNA constructs for wild-type and mutant alleles of CYP26A1 were constructed in a pcDNA3.1 expression vector containing a FLAG tag at the C-terminal end, which was used to identify and quantitate the CYP26A1 allelic proteins when expressed in COS-1 cells. Wild type CYP26A1 protein metabolized all-trans-retinoic acid (at-RA) to 4-oxo-RA, 4-OH-RA and 18-OH-RA as well as watersoluble metabolites. CYP26A1.3 (F186L) and CYP26A1.4 (C358R) allelic proteins exhibited significantly lower metabolism (40-80%) of at-RA than wild-type CYP26A1.1 protein. This study identifies two CYP26A1 coding alleles, CYP26A1*3 and CYP26A1*4, which are predicted to be defective in retinoic acid metabolism based on the metabolism of at-RA by the recombinant proteins. This is the first study to identify coding alleles of CYP26A1. The in vitro characterization of the recombinant allelic proteins suggests the need for future clinical studies of genotype/phenotype relationships of CYP26A1 in embryonic development.

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Vitamin A

Solomons¹

2012

Present Knowledge in Nutrition

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Retinoic acid and retinoid receptors: potential chemopreventive and therapeutic role in cervical cancer

Cited by 81 publications

References 65 publications

Influence of LOX/COX inhibitors on cell differentiation induced by all-trans retinoic acid in neuroblastoma cell lines

Influence of LOX/COX inhibitors on cell differentiation induced by all-trans retinoic acid in neuroblastoma cell lines

The discovery of new coding alleles of human CYP26A1 that are potentially defective in the metabolism of all-trans retinoic acid and their assessment in a recombinant cDNA expression system

Vitamin A

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