Curcumin Inhibits Tumor Growth and Angiogenesis in Ovarian Carcinoma by Targeting the Nuclear Factor-κB Pathway

Abstract

Purpose: Curcumin, a component of turmeric, has been shown to suppress inflammation and angiogenesis largely by inhibiting the transcription factor nuclear factor-nB (NF-nB). 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-nB 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-nB 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-nB 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 multidrugresistant 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.

Curcumin as “Curecumin”: From kitchen to clinic

“…We have found that (a) the combination of curcumin and gemcitabine inhibits pancreatic cancer growth in nude mice by inhibiting NF-kB regulated gene expression, cell proliferation, and angiogenesis [144]; (b) the combination of curcumin and docetaxel is effective against human ovarian cancer in nude mice [142]; (c) curcumin can suppress the growth of human glioblastoma in rodents [77]; and (d) curcumin sensitizes colon cancers in nude mice to oxaliplatin [137]. In addition, other recent studies have shown that curcumin sensitizes prostate cancers to chemotherapeutics and radiation by downregulating expression of the MDM2 oncogene [82].…”

Development and characterization of co-loaded curcumin/triazole-halloysite systems and evaluation of their potential anticancer activity

“…Several studies, also, report that it is an agent possessing a wide variety of biological and pharmacological activities, including anti-proliferation (Choi et al, 2006), antiapoptosis (Aggarwal et al, 2008), anti-angiogenesis (Lin et al, 2007) and inhibition of cell invasion and metastasis (Chen et al, 2008).…”

Relation between menin expression and NF-κB activity in an intestinal cell line

“…Parthenolide is a plantderived sesquiterpene lactone whereas curcumin is a derivative of the spice turmeric (Curcuma longa). Both of them are widely used to inhibit the DNA binding of NF-kB proteins as well as the IkB kinase in cellular or animal tumor models (Oka et al, 2007;Kishida et al, 2007;Lin et al, 2007;Marin et al, 2007). First of all, we demonstrated that inhibition of the NF-kB pathway resulted in the normalization of the transcriptional activity of the cyclin D1 gene promoter in the low-menin expressing AS303 cells.…”