Curcumin Inhibits Tumor Growth and Angiogenesis in Ovarian Carcinoma by Targeting the Nuclear factor-kappaB Pathway

Clin Cancer Res. 2007 Jun 1;13(11):3423-30. doi: 10.1158/1078-0432.CCR-06-3072.

Abstract

Purpose: 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.

Experimental design: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Carcinoma / drug therapy*
  • Carcinoma / pathology
  • Curcumin / pharmacology*
  • Disease Models, Animal
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • NF-kappa B / metabolism*
  • Neoplasm Transplantation
  • Neovascularization, Pathologic*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Platelet Endothelial Cell Adhesion Molecule-1 / biosynthesis

Substances

  • Antineoplastic Agents
  • NF-kappa B
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Curcumin