Role of cytochrome P‐450 genetic polymorphisms in oral carcinogenesis

Hernando-Rodriguez, M.; Rey-Barja, Natalia; Marichalar-Mendía, Xabier; Rodriguez-Tojo, Maria J.; Acha-Sagredo, Amelia; Aguirre‐Urízar, José Manuel

doi:10.1111/j.1600-0714.2011.01067.x

Cited by 25 publications

(19 citation statements)

References 79 publications

(179 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CYP are crucial molecules for tobacco-related oral carcinogenesis [26]. We proposed that CYP may involve in the metabolism of BQ components, transform procarcinogens to DNA-reactive intermediates and contribute to oral cancer.…”

Section: Discussionmentioning

confidence: 99%

Areca Nut Components Affect COX-2, Cyclin B1/cdc25C and Keratin Expression, PGE2 Production in Keratinocyte Is Related to Reactive Oxygen Species, CYP1A1, Src, EGFR and Ras Signaling

et al. 2014

View full text Add to dashboard Cite

AimsChewing of betel quid (BQ) increases the risk of oral cancer and oral submucous fibrosis (OSF), possibly by BQ-induced toxicity and induction of inflammatory response in oral mucosa.MethodsPrimary gingival keratinocytes (GK cells) were exposed to areca nut (AN) components with/without inhibitors. Cytotoxicity was measured by 3-(4,5-dimethyl- thiazol- 2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. mRNA and protein expression was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. PGE2/PGF2α production was measured by enzyme-linked immunosorbent assays.ResultsAreca nut extract (ANE) stimulated PGE2/PGF2α production, and upregulated the expression of cyclooxygenase-2 (COX-2), cytochrome P450 1A1 (CYP1A1) and hemeoxygenase-1 (HO-1), but inhibited expression of keratin 5/14, cyclinB1 and cdc25C in GK cells. ANE also activated epidermal growth factor receptor (EGFR), Src and Ras signaling pathways. ANE-induced COX-2, keratin 5, keratin 14 and cdc25C expression as well as PGE2 production were differentially regulated by α–naphthoflavone (a CYP 1A1/1A2 inhibitor), PD153035 (EGFR inhibitor), pp2 (Src inhibitor), and manumycin A (a Ras inhibitor). ANE-induced PGE2 production was suppressed by piper betle leaf (PBL) extract and hydroxychavicol (two major BQ components), dicoumarol (a NAD(P)H:Quinone Oxidoreductase - NQO1 inhibitor) and curcumin. ANE-induced cytotoxicity was inhibited by catalase and enhanced by dicoumarol, suggesting that AN components may contribute to the pathogenesis of OSF and oral cancer via induction of aberrant differentiation, cytotoxicity, COX-2 expression, and PGE2/PGF2αproduction.ConclusionsCYP4501A1, reactive oxygen species (ROS), EGFR, Src and Ras signaling pathways could all play a role in ANE-induced pathogenesis of oral cancer. Addition of PBL into BQ and curcumin consumption could inhibit the ANE-induced inflammatory response.

show abstract

Section: Discussionmentioning

confidence: 99%

Areca Nut Components Affect COX-2, Cyclin B1/cdc25C and Keratin Expression, PGE2 Production in Keratinocyte Is Related to Reactive Oxygen Species, CYP1A1, Src, EGFR and Ras Signaling

et al. 2014

View full text Add to dashboard Cite

show abstract

“…However, there are several elegant studies that show the involvement of CYP2A6, CYP2A13, CYP1A1 and CYP1B1 in smoking/nicotine-mediated toxicity leading to various types of cancers and hepatic toxicity [38, 39]. The majority of tobacco constituents, including nicotine, are metabolized and/or activated by CYP enzymes to generate ROS and/or reactive metabolites, NNK [40]. ROS and reactive metabolites are known to cause DNA damage, lipid peroxidation and protein oxidation that leads to cell toxicity [41].…”

Section: Mechanism Of Tobacco Smoking Mediated Toxicity: Role Of Cypmentioning

confidence: 99%

Tobacco smoking effect on HIV-1 pathogenesis: role of cytochrome P450 isozymes

Ande

McArthur

Kumar

et al. 2013

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

Introduction Tobacco smoking is highly prevalent among the HIV-1-infected population. In addition to diminished immune response, smoking has been shown to increase HIV-1 replication and decrease response to antiretroviral therapy, perhaps through drug–drug interaction. However, the mechanism by which tobacco/nicotine increases HIV-1 replication and mediates drug–drug interaction is poorly understood. Areas covered In this review, the authors discuss the effects of smoking on HIV-1 pathogenesis. Since they propose a role for the cytochrome P450 (CYP) pathway in smoking-mediated HIV-1 pathogenesis, the authors briefly converse the role of CYP enzymes in tobacco-mediated oxidative stress and toxicity. Finally, the authors focus on the role of CYP enzymes, especially CYP2A6, in tobacco/nicotine metabolism and oxidative stress in HIV-1 model systems monocytes/macrophages, lymphocytes, astrocytes and neurons, which may be responsible for HIV-1 pathogenesis. Expert opinion Recent findings suggest that CYP-mediated oxidative stress is a novel pathway that may be involved in smoking-mediated HIV-1 pathogenesis, including HIV-1 replication and drug–drug interaction. Thus, CYP and CYP-associated oxidative stress pathways may be potential targets to develop novel pharmaceuticals for HIV-1-infected smokers. Since HIV-1/TB co-infections are common, future study involving interactions between antiretroviral and antituberculosis drugs that involve CYP pathways would also help treat HIV-1/TB co-infected smokers effectively.

show abstract

“…Betel quid chewing generate a high amount of ROS, which has been implicated in multistage carcinogenesis (Soya et al, 2007). Recent studies reported a significant association between CYP1A1 polymorphism and HNC among tobacco-betel quid chewers (Anantharaman et al, 2007;Hernando-Rodriguez et al, 2012;Chaudhuri et al, 2013), whereas few studies did not found any relationship between CYP1A1 and chewing (Khlifi et al, 2014).…”

Section: Discussionmentioning

confidence: 99%