Inhibitory Effects of Curcumin on Carcinogenesis in Mouse Epidermis

Huang, Mou‐Tuan; Robertson, Fredika M.; Lysz, Thomas W.; Ferraro, Thomas; Wang, Zhi Yuan; Georgiadis, Constantine A.; Laskin, Jeffrey D.; Conney, Allan H.

doi:10.1021/bk-1992-0507.ch027

Cited by 200 publications

(249 citation statements)

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“…However, the levels of curcumin recovered were below 10 À8 M, thus of an order of magnitude that is unlikely to exert pharmacological effects in the light of results obtained in experiments in which cells in vitro were exposed to curcumin (see e.g., Sharma, 1976;Kunchandy and Rao, 1990;Huang et al, 1991;Reddy and Lokesh, 1992;Tonessan and Greenhill, 1992;Subramanian et al, 1994;Plummer et al, 1999).…”

Section: Discussionmentioning

confidence: 98%

“…Other mechanisms by which curcumin may exert chemopreventive action are interference with the transcription of the enzyme cyclooxygenase-2 (COX-2) (Plummer et al, 1999), induction of apoptosis (Kuo et al, 1996;Kawamori et al, 1999) and antiangiogenesis (Arbiser et al, 1998). The concentrations of curcumin needed to exert these effects in cells in vitro, range from 5 to 50 mM (Sharma, 1976;Kunchandy and Rao, 1990;Huang et al, 1991;Tonessan and Greenhill, 1992;Reddy and Lokesh, 1992;Subramanian et al, 1994;Plummer et al, 1999). Little is known about the potential pharmacological efficacy of products of the metabolic conjugation and reduction of curcumin.…”

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confidence: 99%

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Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration

et al. 2004

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Studies in vitro and in animal models of colorectal and hepatocellular cancers suggest that curcumin is an effective chemopreventive agent. In this pilot trial, we investigated whether oral administration of curcumin results in concentrations of the agent in normal and malignant human liver tissue, which are sufficient to elicit pharmacological activity. In total, 12 patients with hepatic metastases from colorectal cancer received 450 -3600 mg of curcumin daily, for 1 week prior to surgery. Levels of curcumin and its metabolites were measured by HPLC in portal and peripheral blood, bile and liver tissue. Curcumin was poorly available, following oral administration, with low nanomolar levels of the parent compound and its glucuronide and sulphate conjugates found in the peripheral or portal circulation. While curcumin was not found in liver tissue, trace levels of products of its metabolic reduction were detected. In patients who had received curcumin, levels of malondialdehyde-DNA (M 1 G) adduct, which reflect oxidative DNA changes, were not decreased in post-treatment normal and malignant liver tissue when compared to pretreatment samples. The results suggest that doses of curcumin required to furnish hepatic levels sufficient to exert pharmacological activity are probably not feasible in humans.

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Section: Discussionmentioning

confidence: 98%

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confidence: 99%

Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration

et al. 2004

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“…Curcumin can reportedly suppress the tumorigenic activity of a wide variety of carcinogens in cancers of the colon, duodenum, esophagus, forestomach, stomach, liver, breast, leukemia, oral cavity, and prostate. In studies in mice, curcumin was able to inhibit 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor formation [31,120,126]. Curcumin has also shown an ability to inhibit the mammary tumor-initiating activity of DMBA [110] and the in vivo formation of mammary DMBA-DNA adducts in female rats [111] and to exert chemopreventive activity when administered during the promotion/progression stage of colon carcinogenesis [91].…”

Section: Curcumin Is a Potent Chemopreventive Agentmentioning

confidence: 99%

Curcumin as “Curecumin”: From kitchen to clinic

Goel

Kunnumakkara

Aggarwal

2008

Biochemical Pharmacology

1,919

1,290

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“…Extensive research within the last half-a-decade has confirmed that curcumin mediates anti-inflammatory effects through the downregulation of transcription factor nuclear factor-κB (NF-κB) [1,2] tumor necrosis factor (TNF) [3], interleukin-6 (IL-6) [4], interleukin-8 (IL-8) [5], adhesion molecules [6], inducible nitric oxide synthase (iNOS) [7], matrix metalloproteinase-9 (MMP-9) [8], cyclooxygenase-2 (COX-2) [9], and 5-lipoxygenase (5-LOX) [10]. In fact, curcumin has been shown to bind to an active site in 5-LOX, and the two together have been cocrystallized [11].…”

Section: Introductionmentioning

confidence: 99%

Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane)

Sandur

Ichikawa

Pandey

et al. 2007

Free Radical Biology and Medicine

272

172

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Extensive research within last half a century has indicated that curcumin (diferuloylmethane), a yellow pigment in curry powder, exhibits antioxidant, anti-inflammatory and proapoptotic activities. Whether anti-inflammatory and proapoptotic activities assigned to curcumin, are mediated through its antioxidant mechanism was investigated. We found that TNF-mediated NF-κB activation was inhibited by curcumin; and glutathione reversed the inhibition. Similarly, suppression of TNFinduced AKT activation by curcumin, was also abrogated by glutathione. The reducing agent also counteracted the inhibitory effect of curcumin on TNF-induced NF-κB regulated antiapoptotic (Bcl-2, Bcl-xL, IAP1), proliferative (cyclin D1) and proinflammatory (COX-2, iNOS and MMP-9) gene products. The suppression of TNF-induced AP-1 activation by curcumin was also reversed by glutathione. Also, the direct proapoptotic effects of curcumin were inhibited by glutathione and potentiated by depletion of intracellular glutathione by buthionine sulfoximine. Moreover, curcumin induced the production of reactive oxygen species (ROS) and modulated the intracellular GSH levels. Quenchers of hydroxyl radicals, however, were ineffective in inhibiting curcumin mediated NF-κB suppression. Further, N-acetylcysteine partially reversed the effect of curcumin. Based on these results we conclude that curcumin mediate its apoptotic and anti-inflammatory activities through modulation of the redox status of the cell.

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Inhibitory Effects of Curcumin on Carcinogenesis in Mouse Epidermis

Cited by 200 publications

References 0 publications

Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration

Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration

Curcumin as “Curecumin”: From kitchen to clinic

Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane)

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