Evaluation of benzyl selenocyanate glutathione conjugate for potential chemopreventive properties in colon carcinogenesis.

Kawamori, Toshihiko; El‐Bayoumy, Karam; Ji, Ben Yi; Rodriguez, Jose G.; Rao, Chinthalapally V.; Reddy, Bandaru S.

doi:10.3892/ijo.13.1.29

Cited by 20 publications

(18 citation statements)

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“…Genetic knock-out or pharmacological inhibition of COX2 has been shown to protect against development of colonic tumours in mice which harbour a germline knock-out mutation of the adenomatous polyposis coli (APC) tumour suppressor gene, or in rats exposed to the colon carcinogen azoxymethane (Oshima et al, 1996;Kawamori et al, 1998). Germline and somatic mutations in the APC gene are important early events in human colon carcinogenesis (Nishisho et al, 1991;Powell et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-κB activation via the NIK/IKK signalling complex

et al. 1999

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Colorectal cancer is a major cause of cancer deaths in Western countries, but epidemiological data suggest that dietary modi®cation might reduce these by as much as 90%. Cyclo-oxygenase 2 (COX2), an inducible isoform of prostaglandin H synthase, which mediates prostaglandin synthesis during in¯ammation, and which is selectively overexpressed in colon tumours, is thought to play an important role in colon carcinogenesis. Curcumin, a constituent of turmeric, possesses potent anti-in¯amma-tory activity and prevents colon cancer in animal models. However, its mechanism of action is not fully understood. We found that in human colon epithelial cells, curcumin inhibits COX2 induction by the colon tumour promoters, tumour necrosis factor a or fecapentaene-12. Induction of COX2 by in¯ammatory cytokines or hypoxia-induced oxidative stress can be mediated by nuclear factor kappa B (NF-kB). Since curcumin inhibits NF-kB activation, we examined whether its chemopreventive activity is related to modulation of the signalling pathway which regulates the stability of the NF-kBsequestering protein, IkB. Recently components of this pathway, NF-kB-inducing kinase and IkB kinases, IKKa and b, which phosphorylate IkB to release NF-kB, have been characterised. Curcumin prevents phosphorylation of IkB by inhibiting the activity of the IKKs. This property, together with a long history of consumption without adverse health e ects, makes curcumin an important candidate for consideration in colon cancer prevention.

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Section: Introductionmentioning

confidence: 99%

Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-κB activation via the NIK/IKK signalling complex

et al. 1999

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“…Effects on inactivation and chemoprotective enzymes have received the greatest attention. Reported investigations include studies with phenylenebis(methylene)selenocyanate isomers (Reddy et al, 1992, Tanaka et al, 1997, Sohn et al, 1999, Prokopczyk et al, 2000, benzylselenocyanate, and its glutathione conjugate (Kawamori et al, 1998), and diphenylmethylselenocyanate (Ghosh et al, 2005, Das and. Effects on bioactivation enzyme activities (cytochrome P450s) were investigated for phenylenebis (methylene)selenocyanate isomers (Sohn et al, 1999, Prokopczyk et al, 2000 following demonstration of their inhibitory activity in vitro (Shimada et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Murine hepatoma (Hepa1c1c7) cells: A responsive in vitro system for chemoprotective enzyme induction by organoselenium compounds

El‐Sayed

Aboul‐Fadl

Roberts

et al. 2007

Toxicology in Vitro

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Murine (Hepa1c1c7) hepatoma cells are a suitable in vitro system for investigating the regulation of chemoprotective enzymes by selenazolidines, novel L-selenocysteine prodrugs developed as potential chemopreventive agents. They are less sensitive to the cytotoxic effects of both selenite and the less toxic selenazolidines than rat hepatoma (H4IIE) cells. All four selenazolidine 4-carboxylic acid (SCA) derivatives examined elevated thioredoxin reductase (Txnrd1), alpha-class glutathione transferases (Gsta), and UDP-glucuronosyltransferase (Ugt)1a6 mRNAs. NAD(P)Hquinone oxidoreductase (Nqo1) was induced by the three 2-alkyl derivatives (2-cyclohexylSCA, 2-butylSCA, and 2-methylSCA) but not SCA itself. Transcripts of mu-and pi-class glutathione transferases were induced only by 2-cyclohexylSCA and 2-butylSCA. Only Gsta and Txnrd1 transcripts were elevated by L-selenomethionine, L-selenocystine, or Se-methyl-L-selenocysteine. Txnrd1, Gsta, Nqo1, and Gstp responses to selenazolidines were all abolished by actinomycin D while Ugt1a6 responses were not. Induction responses to the selenazolidines were also eliminated (most) or reduced (Txnrd1 by 2-methylSCA) by cycloheximide, with the exception of Ugt1a6. The Ugt1a6 mRNA levels in the presence of SCAs and cycloheximide were similar to those with cycloheximide alone, and were almost double those of vehicle-treated cells. Thus, Hepa1c1c7 cells appear to provide a viable platform for the study of protective enzyme regulation by selenocompounds, and with the exception of Ugt1a6, the mRNA elevations from selenazolidines are transcriptionally dependent.

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“…For instance, COX-2 inhibitors have been shown to inhibit proliferation of colon cancer cell and inhibit the formation of colorectal cancers in animal models through induction of apoptosis (Kawamori et al, 1998;Sheng et al, 1998;Reddy et al, 1996). Besides colorectal cancers, COX-2 inhibitors also suppress tumor growth in nude mice bearing gastric cancer xenografts by induction of apoptosis .…”

Section: Introductionmentioning

confidence: 99%

Novel target for induction of apoptosis by cyclo-oxygenase-2 inhibitor SC-236 through a protein kinase C-β1-dependent pathway

et al. 2002

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Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of gastrointestinal cancers. Recently, a similar protective effect has been demonstrated by the specific cyclo-oxygenase-2 (COX-2) inhibitors. However, the exact mechanism that accounts for the anti-proliferative effect of specific COX-2 inhibitors is still not fully understood, and it is still controversial whether these protective effects are predominantly mediated through the inhibition of COX-2 activity and prostaglandin synthesis. Identification of molecular targets regulated by COX-2 inhibitors could lead to a better understanding of their pro-apoptotic and anti-neoplastic activities. In the present study, we investigated the effect and the possible molecular target of a COX-2-specific inhibitor SC-236 on gastric cancer. We showed that SC-236 induced apoptosis in gastric cancer cells. However, this effect was not dependent on COX-2 inhibition. SC-236 down-regulated the protein expression and kinase activity of PKC-b 1 , increased the expression of PKCd and PKCZ, but did not alter the expression of other PKC isoforms in AGS cells. Moreover, exogenous prostaglandins or PGE 2 receptor antagonists could not reverse the inhibition effect on PKCb 1 by SC-236, which suggested that this effect occurred through a mechanism independent of cyclo-oxygenase activity and prostaglandin synthesis. Overexpression of PKCb 1 attenuated the apoptotic response of AGS cells to SC-236 and was associated with overexpression of p21 waf1/cip1 . Inhibition of PKCb 1 -mediated overexpression of p21 waf1/cip1 partially reduced the anti-apoptotic effect of PKCb 1 . The down-regulation of PKCb 1 provides an explanation for COX-independent apoptotic effects of specific COX-2 inhibitor in cultured gastric cancer cells. We also suggest that PKCb 1 act as survival mediator in gastric cancer, and its down-regulation by COX-2 inhibitor SC-236 may provide new target for future treatment of gastric cancer.

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Evaluation of benzyl selenocyanate glutathione conjugate for potential chemopreventive properties in colon carcinogenesis.

Cited by 20 publications

References 0 publications

Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-κB activation via the NIK/IKK signalling complex

Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-κB activation via the NIK/IKK signalling complex

Murine hepatoma (Hepa1c1c7) cells: A responsive in vitro system for chemoprotective enzyme induction by organoselenium compounds

Novel target for induction of apoptosis by cyclo-oxygenase-2 inhibitor SC-236 through a protein kinase C-β1-dependent pathway

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