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Anticancer potential of curcumin - Norma Jones Houston Myeloma PDF

52 Pages·2003·0.36 MB·English
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Anticancer potential of curcumin Bharat B. Aggarwal, Ph.D. Cytokine Research Section, Department of Bioimmunotherapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, U.S.A. Source of Curcumin Turmeric (Curcuma longa) Structure of curcumin O O CH3O OCH3 Curcumin I (77%) HO OH O O Curcumin II OCH3 Demethoxycurcumin (17%) HO OH O O Curcumin III Bis-Demethoxycurcumin (3%; less active) HO OH Different stages of cancer progression and its suppression by curcumin Constitutive activation of Overexpression of Overexpression of transcription factors (cid:190)Oncogenes (cid:190)Matrix metalloproteases (cid:190)HER2 (cid:190)Cyclooxygenase-2 (cid:190)AP-1& NF-κB (cid:190)Growth factors (cid:190)Adhesion molecules (e.g; EGF, PDGF, FGF) (cid:190)Chemokine (cid:190)Tumor Suppressor genes (cid:190)Growth factor receptors (cid:190)TNF (cid:190)Survival factors (e.g; Survivin,Bcl-2 and Bcl-xl) (cid:190)Cyclin D1 (cid:190)Decoy receptor Transformation Proliferation Invasion Normal Tumor Tumor Tumor cells cells growth Metastasis curcumin Activation of transcription factor Nuclear Factor-kappa B is suppressed by curcumin Singh S, and Aggarwal BB. J Biol Chem. 1995 Oct 20;270 (42):24995-5000. Role of NF-κB in Development of Cancer Anti-apoptosis/survival Tumor promotion e.g; bcl-xl, cIAP, survivin, cFLIP, e.g; COX2, iNOS, MMP-9, uPA TRAF, SOD, γ-GCS Inflammation Proliferation NF-κB TNF, IL-1, Chemokines e.g; TNF, IL-1, IL-6 Angiogenesis VEGF, TNF, IL-1, IL-8 Metastasis e.g; ICAM-1, VCAM-1, ELAM-1 Curcumin inhibits constitutive NF- κB, IκBα kinase, inhibits proliferation, and induces apoptosis in human multiple myeloma cells Bharti A., Donato N., Singh S., Aggarwal B.B. BLOOD, 101, 2003, 1053-1062 Curcumin Inhibits Constitutive and Interleukin-6-Inducible STAT3 Phosphorylation in Human Multiple Myeloma Cells Alok C. Bharti, Nicholas Donato, and Bharat B. Aggarwal Journal of Immunology, in press) ( Nuclear Factor-κB and STAT3 are Constitutively Active in CD138+ Cells Derived from Multiple Myeloma Patients and Their Suppression Leads to Apoptosis Alok C. Bharti, James M. Reuben, Donna Weber, Raymond Alexanian, Moshe Talpaz and Bharat B. Aggarwal (submitted)

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Anticancer potential of curcumin Bharat B. Aggarwal, Ph.D. Cytokine Research Section, Department of Bioimmunotherapy, The University of Texas M.D. Anderson Cancer Center,
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