Dietary Supplementation of Curcumin Enhances Antioxidant and Phase II Metabolizing Enzymes in ddY Male Mice: Possible Role in Protection against Chemical Carcinogenesis and Toxicity

Iqbal, Mohammad; Sharma, Som D.; Okazaki, Yasumasa; Fujisawa, Masayoshi; Okada, Shigeru

doi:10.1034/j.1600-0773.2003.920106.x

Cited by 265 publications

(157 citation statements)

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“…The resistance to the quinone toxicity for cells treated with resveratrol and other natural polyphenols has been attributed to the increased expression of antioxidant and phase-II metabolizing enzymes (10), such as catalase, GST, and quinone reductases (11,27,37).…”

Section: Similar Properties Of Cells With Qr2 Knockdown and Cells Trementioning

confidence: 99%

“…After centrifugation, the protein contents in the supernatants were normalized by BioRad protein assays. The enzymatic activity assays were performed as described (27) with modification, except the total NAD(P)H-dependent quinone reductase assays, which were adopted from Chen et al (28). Briefly, glucose-6-phosphate dehydrogenase activity is measured by the reduction of NADP.…”

Section: Antioxidant and Phase II Detoxification Enzyme Assaysmentioning

confidence: 99%

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Crystal Structure of Quinone Reductase 2 in Complex with Resveratrol^,

et al. 2004

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Resveratrol has been shown to have chemopreventive, cardioprotective, and antiaging properties. Here, we report that resveratrol is a potent inhibitor of quinone reductase 2 (QR2) activity in vitro with a dissociation constant of 35 nM and show that it specifically binds to the deep active-site cleft of QR2 using high-resolution structural analysis. All three resveratrol hydroxyl groups form hydrogen bonds with amino acids from QR2, anchoring a flat resveratrol molecule in parallel with the isoalloxazine ring of FAD. The unique active-site pocket in QR2 could potentially bind other natural polyphenols such as flavonoids, as proven by the high affinity exhibited by quercetin toward QR2. K562 cells with QR2 expression suppressed by RNAi showed similar properties as resveratrol-treated cells in their resistance to quinone toxicity. Furthermore, the QR2 knockdown K562 cells exhibit increased antioxidant and detoxification enzyme expression and reduced proliferation rates. These observations could imply that the chemopreventive and cardioprotective properties of resveratrol are possibly the results of QR2 activity inhibition, which in turn, upregulates the expression of cellular antioxidant enzymes and cellular resistance to oxidative stress.Resveratrol (trans-3,4′,5-trihydroxystilbene) is a phyto-polyphenol that occurs in grapes and a variety of medicinal plants. Because of its abundance in grapes, it is present in significant amount in grape products such as grape juice and wines, particularly red wine (1). The revealing of resveratrol as a cancer chemopreventive agent in 1997 (2) sparked extensive research on its chemopreventive properties (3). Resveratrol has been tested on a variety of cancers in animal model studies. As in the case of the 1997 study, Jang et al. (2) demonstrated in a mouse model that resveratrol is effective in prevention of DMBA-(dimethylbenzanthracene) and TPA-(tetradecanoylphorbol-13-acetate) induced skin cancer. Application of 1, 5, 10, or 25 µM of resveratrol with TPA twice a week for 18 weeks reduced the number of skin tumors per mouse by 68, 81, 76, or 98%, respectively, and the percentage of mice with tumors was lowered by 50, 63. 63, or 88%. In mouse models of colon cancer and small intestinal cancer, resveratrol prevents cancer formation with 100 and 70% efficacy, respectively (4, 5). † This work was supported in part by National Institute of Health Grant R21 CA104424. ‡ The atomic coordinates and structure factors (PDB code 1SG0) NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptResveratrol has been suggested to block the multistep process of carcinogenesis, namely, tumor initiation, promotion, and progression (3). Despite extensive investigation, no clear molecular basis for the actions of resveratrol has emerged. A variety of hypotheses have been proposed to explain its functions: antioxidant effects, proapoptotic effects, cell-cycle regulation, inhibition of protein kinases, regulation of NFκB and Iκ3, and modulation of estrogen effects (3, 6). ...

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Section: Similar Properties Of Cells With Qr2 Knockdown and Cells Trementioning

confidence: 99%

Section: Antioxidant and Phase II Detoxification Enzyme Assaysmentioning

confidence: 99%

Crystal Structure of Quinone Reductase 2 in Complex with Resveratrol^,

et al. 2004

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“…Keberadaan gugusan phenolik pada ketiga senyawa tersebut dilaporkan juga menyebabkan aktivitas antioksidan yang kuat pada system biologis (Ahsan, 1998), sehingga dapat mencegah penyakit-penyakit yang berhubungan dengan reaksi peroksidasi. Bahkan, Institut Nasional Kanker telah mencoba mengembangkan bahan ini dalam uji klinis anti kanker (Kelloff, 2000), dan penelitian-penelitian praklinis lain terus dilakukan terhadap sel kanker yang lain (Iqbal, 2003).…”

Section: (Cahyono Dkk) Pendahuluanunclassified

PENGARUH PROSES PENGERINGAN RIMPANG TEMULAWAK (Curcuma xanthorriza ROXB) TERHADAP KANDUNGAN DAN KOMPOSISI KURKUMINOID

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Limantara

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“…67 Moreover, administration of curcumin has been found to increase expression of the xenobiotic detoxifying enzymes in both liver and kidney of mice. 68 …”

Section: Curcuminmentioning

confidence: 99%