title: Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-kappaB pathway.
abstract: OBJECTIVE
  Curcumin, a component of turmeric, has been shown to suppress inflammation and angiogenesis largely by inhibiting the transcription factor nuclear factor-kappaB (NF-kappaB). This study evaluates the effects of curcumin on ovarian cancer growth using an orthotopic murine model of ovarian cancer.
  
  
  METHODS
  In vitro and in vivo experiments of curcumin with and without docetaxel were done using human ovarian cancer cell lines SKOV3ip1, HeyA8, and HeyA8-MDR in athymic mice. NF-kappaB modulation was ascertained using electrophoretic mobility shift assay. Evaluation of angiogenic cytokines, cellular proliferation (proliferating cell nuclear antigen), angiogenesis (CD31), and apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) was done using immunohistochemical analyses.
  
  
  RESULTS
  Curcumin inhibited inducible NF-kappaB activation and suppressed proliferation in vitro. In vivo dose-finding experiments revealed that 500 mg/kg orally was the optimal dose needed to suppress NF-kappaB and signal transducers and activators of transcription 3 activation and decrease angiogenic cytokine expression. In the SKOV3ip1 and HeyA8 in vivo models, curcumin alone resulted in 49% (P = 0.08) and 55% (P = 0.01) reductions in mean tumor growth compared with controls, whereas when combined with docetaxel elicited 96% (P < 0.001) and 77% reductions in mean tumor growth compared with controls. In mice with multidrug-resistant HeyA8-MDR tumors, treatment with curcumin alone and combined with docetaxel resulted in significant 47% and 58% reductions in tumor growth, respectively (P = 0.05). In SKOV3ip1 and HeyA8 tumors, curcumin alone and with docetaxel decreased both proliferation (P < 0.001) and microvessel density (P < 0.001) and increased tumor cell apoptosis (P < 0.05).
  
  
  CONCLUSIONS
  Based on significant efficacy in preclinical models, curcumin-based therapies may be attractive in patients with ovarian carcinoma.
authors.affiliation: Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yvonne G
authors.initials: YG
authors.lastname: Lin
authors.forename: Ajaikumar B
authors.initials: AB
authors.lastname: Kunnumakkara
authors.forename: Asha
authors.initials: A
authors.lastname: Nair
authors.forename: William M
authors.initials: WM
authors.lastname: Merritt
authors.forename: Liz Y
authors.initials: LY
authors.lastname: Han
authors.forename: Guillermo N
authors.initials: GN
authors.lastname: Armaiz-Pena
authors.forename: Aparna A
authors.initials: AA
authors.lastname: Kamat
authors.forename: Whitney A
authors.initials: WA
authors.lastname: Spannuth
authors.forename: David M
authors.initials: DM
authors.lastname: Gershenson
authors.forename: Susan K
authors.initials: SK
authors.lastname: Lutgendorf
authors.forename: Bharat B
authors.initials: BB
authors.lastname: Aggarwal
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D003474:Curcumin