Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma. - GreenMedInfo Summary
Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-kappaB pathway.
J Clin Invest. 2009 May;119(5):1322-34. doi: 10.1172/JCI37385. Epub 2009 Apr 20. PMID: 17545551
Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
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.