Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-κB pathway

Yvonne G. Lin, Ajaikumar B. Kunnumakkara, Asha Nair, William M. Merritt, Liz Y. Han, Guillermo N. Armaiz-Pena, Aparna A. Kamat, Whitney A. Spannuth, David M. Gershenson, Susan K. Lutgendorf, Bharat B. Aggarwal, Anil K. Sood

Research output: Contribution to journalArticlepeer-review

325 Scopus citations

Abstract

Purpose: Curcumin, a component of turmeric, has been shown to suppress inflammation and angiogenesis largely by inhibiting the transcription factor nuclear factor-κB (NF-κB). 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-κB 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-κB 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-κB 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 preclinicalmodels, curcumin-based therapies may be attractive in patients with ovarian carcinoma.

Original languageEnglish (US)
Pages (from-to)3423-3430
Number of pages8
JournalClinical Cancer Research
Volume13
Issue number11
DOIs
StatePublished - Jun 1 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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