Celecoxib, a cyclooxygenase-2 inhibitor, prevents induction of liver preneoplastic lesions in rats

Márquez-Rosado, Lucrecia; Trejo-Solís, María Cristina; García-Cuéllar, Claudia M.; Villa‐Treviño, Saúl

doi:10.1016/j.jhep.2005.02.032

Cited by 41 publications

(38 citation statements)

References 31 publications

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“…Interestingly, COX-2-independent effects of celecoxib have also been observed during hepatocarcinogenesis in vivo. In the study by Marquez-Rosado [64] neither COX-2 expression nor PGE2 production were altered by celecoxib treatment, suggesting that celecoxib effects are mediated by COX-2/PGE2-independent mechanisms.…”

Section: Cox Inhibitors In Hepatocellular Carcinomamentioning

confidence: 82%

“…In the rat model of choline-deficient, L-amino acid-defined diet (CDAA)-induced hepatocarcinogenesis the administration of aspirin or nimesulide with the diet decreased the number of preneoplastic and neoplastic nodules [60,63] . In a recent study by Marquez-Rosado [64] treatment with celecoxib was highly effective in inhibiting the multiplicity and size of liver preneoplastic lesions induced by DEN, 2-AAF and partial hepatectomy.…”

Section: Cox Inhibitors In Hepatocellular Carcinomamentioning

confidence: 96%

“…Evidence from animal models Experimental studies on animal models of liver cancer have shown that NSAIDs, including both selective and non-selective COX-2 inhibitors, exert chemopreventive as well as therapeutic effects [59][60][61][62][63][64] . In the rat model of choline-deficient, L-amino acid-defined diet (CDAA)-induced hepatocarcinogenesis the administration of aspirin or nimesulide with the diet decreased the number of preneoplastic and neoplastic nodules [60,63] .…”

Section: Cox Inhibitors In Hepatocellular Carcinomamentioning

confidence: 99%

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Cyclooxygenases in hepatocellular carcinoma

Cervello¹,

Montalto²

2006

WJG

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M a n y e p i d e m i o l o g i c a l s t u d i e s d e m o n s t r a t e t h a t treatment with non-steroidal anti-inflammatory drugs(NSAIDs) reduce the incidence and mortality of certain malignancies, especially gastrointestinal cancer. The cyclooxygenase (COX) enzymes are well-known targets of NSAIDs. However, conventional NSAIDs nonselectively inhibit both the constitutive form COX-1, and the inducible form COX-2. Recent evidence indicates that COX-2 is an important molecular target for anticancer therapies. Its expression is undetectable in most normal tissues, and is highly induced by proinflammatory cytokines, mitogens, tumor promoters and growth factors. It is now well-established that COX-2 is chronically overexpressed in many premalignant, m a l i g n a n t , a n d m e t a s t a s t i c c a n c e r s , i n c l u d i n g hepatocellular carcinoma (HCC). Overexpression of COX-2 in patients with HCC is generally higher in welldifferentiated HCCs compared with less-differentiated H C C s o r h i s t o l o g i c a l l y n o r m a l l i v e r , s u g g e s t i n g that COX-2 may be involved in the early stages of hepatocarcinogenesis, and increased expression of COX-2 in noncancerous liver tissue has been significantly associated with shorter disease-free survival in patients with HCC.In tumors, overexpression of COX-2 leads to an increase in prostaglandin (PG) levels, which affect many mechanisms involved in carcinogenesis, such as angiogenesis, inhibition of apoptosis, stimulation of cell growth as well as the invasiveness and metastatic potential of tumor cells.The availability of novel agents that selectively inhibit COX-2 (COXIB), has contributed to shedding light on the role of this molecule. Experimental studies on animal models of liver cancer have shown that NSAIDs, including both selective and non-selective COX-2 inhibitors, exert chemopreventive as well as therapeutic effects. However, the key mechanism by which COX-2 inhibitors affect HCC cell growth is as yet not fully understood.Increasing evidence suggests the involvement of molecular targets other than COX-2 in the antiproliferative effects of COX-2 selective inhibitors. Therefore, COX-inhibitors may use both COX-2-dependent and COX-2-independent mechanisms to mediate their antitumor properties, although their relative contributions toward the in vivo effects remain less clear.Here we review the features of COX enzymes, t h e r o l e o f t h e e x p r e s s i o n o f C O X i s o f o r m s i n hepatocarcinogenesis and the mechanisms by which they may contribute to HCC growth, the pharmacological properties of COX-2 selective inhibitors, the antitumor effects of COX inhibitors, and the rationale and feasibility of COX-2 inhibitors for the treatment of HCC.

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Section: Cox Inhibitors In Hepatocellular Carcinomamentioning

confidence: 82%

Section: Cox Inhibitors In Hepatocellular Carcinomamentioning

confidence: 96%

Section: Cox Inhibitors In Hepatocellular Carcinomamentioning

confidence: 99%

See 1 more Smart Citation

Cyclooxygenases in hepatocellular carcinoma

Cervello¹,

Montalto²

2006

WJG

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“…Other HCC associated targets, such as epidermal growth factor (EGF) signaling (Hampton, 2007), telomerase (Djojosubroto et al, 2005) and cyclooxygenase (Márquez-Rosado et al, 2005), were studied intensively with regard to their therapeutic effects. However, the benefits are far from satisfactory, so there is still a need to identify new therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Novel Therapeutic Targets for Hepatocellular Carcinoma Treatment

Chen¹,

Li²

2012

Hepatocellular Carcinoma - Basic Research

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“…The proposed mechanisms for the effects of CXB in these models include inhibition of cell proliferation, reduction of angiogenesis and induction of apoptosis [7] . Recently, we have demonstrated that CXB acts as a chemopreventive agent against the development of preneoplastic lesions induced by diethylnitrosamine (DEN), 2-acetylaminofluorene and partial hepatectomy in the modified resistant hepatocyte (MRH) model [8] . However, the exact mechanism of action by which CXB decreases liver preneoplastic lesions remains unclear, because there was no evidence of apoptosis or of changes in COX-2 expression or PGE2 production after CXB treatment.…”

Section: Introductionmentioning

confidence: 99%

Celecoxib enhances the detoxification of diethylnitrosamine in rat liver cancer

Salcido-Neyoy¹,

Sierra-Santoyo²,

Beltrán-Ramírez³

et al. 2009

WJG

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AIM:To study the effect of celecoxib (CXB) on diethylnitrosamine activation through the regulation of cytochrome P450 in a hepatocarcinogenesis model. METHODS:Six-week-old male Sprague-Dawley rats were randomly divided into five groups, a nontreated group (NT), a diethylnitrosamine-treated group (DEN), a DEN+CXB-treated group (DEN+CXB), and CXB 8 d-treated and CXB 32 d-treated groups. The effects of celecoxib on the enzymatic activities of CYP1A1, 2A, 2B1/2, and 2E1 were assessed in hepatic microsomes 24 h after DEN administration. Changes in CYP1A1 and CYP2B1/2 protein expression were also evaluated. The rate of DEN metabolism was measured by the production of the deethylation metabolite acetaldehyde, and the denitrosation metabolite nitrite.RESULTS: DEN+CXB administration produced a significant increase in the enzymatic activities of CYP2B1/2 and 1A1, whereas it did not change the activities of CYP2A and 2E1, compared to that of the DEN group. CXB treatment for eight days did not produce a significant effect on enzymatic activity when compared to the NT group; however, when it was administered for prolonged times (CXB 32 d group), the enzymatic activities were increased in a similar pattern to those in the DEN+CXB group. The observed increase in the enzymatic activities in the DEN+CXB group was accompanied by an increase in the CYP2B1/2 protein levels; no changes were observed in the levels of CYP1A1. In vitro , CXB increased the denitrosation of DEN, a pathway of metabolic detoxification. The addition of SKF-525A, a preferential inhibitor of CYP2B, abrogated the denitrosation of DEN. CONCLUSION:These results suggest that the mechanism of action of CXB involves enhancement of the detoxification of DEN by an increasing denitrosation via CYP2B1/2.

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Celecoxib, a cyclooxygenase-2 inhibitor, prevents induction of liver preneoplastic lesions in rats

Cited by 41 publications

References 31 publications

Cyclooxygenases in hepatocellular carcinoma

Cyclooxygenases in hepatocellular carcinoma

Novel Therapeutic Targets for Hepatocellular Carcinoma Treatment

Celecoxib enhances the detoxification of diethylnitrosamine in rat liver cancer

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