Abstract 5445: Polyphenolic phytochemical curcumin suppresses HER-2 protein phosphorylation and gene expression in breast cancer cells

Abstract

Abstract Curcumin (diferuloylmethane) is the major pigment ingredient of turmeric, a plant native to South Asia, belonging to ginger family. Turmeric is used in Oriental cuisine and is believed to exert anti-inflammatory, anti-oxidant and anti-carcinogenic properties. Curcumin has apoptotic activity against different types of cancer, including colon cancer, stomach and skin tumors, breast cancer and prostate cancer, and has been the subject of several clinical studies. Curcumin disrupts different stages of carcinogenesis, including cell proliferation, survival, angiogenesis and metastasis in preclinical models. In order to understand the mechanism of action of curcumin in HER-2 positive breast cancer, we investigated the effects of different concentrations of curcumin on SK-BR-3, an HER-2 positive human breast cancer cell line. Curcumin inhibited the growth of SK-BR-3 cells in a concentration- and time-dependent manner, with an IC50 value of 5 ± 1 µg. A significant 80% cells underwent apoptosis in the presence of 25 µM curcumin at the 24 hour of treatment, as determined by APO-BRDU assay. At 25 µM concentration, curcumin suppressed the expression of HER-2 gene by a significant 70% (P ≤ 0.005, compared to untreated control) at 24 hours of treatment, as measured by real-time qPCR assay. In addition, curcumin suppressed the expression of cyclin A, cyclin B1, cyclin D1 and cyclin E by 30 to 70%. In contrast, 10, 25 and 50 µM concentrations of curcumin increased the expression of p21 by 4-, 3-, and 2-fold, respectively, at 16 hours of treatment. Comparable increase in p21 level was evident at 24 hours of treatment also. Curcumin arrested cells in the G2/M phase (38 ± 3% compared to 22 ± 2 % control at the same time point; P < 0.001; n = 3). Curcumin suppressed HER-2 phosphorylation in a concentration- and time-dependent manner, suggesting a possible mechanism of action. Pre-treatment of cells with an anti-oxidant, glutathione partially reversed apoptosis induced by curcumin, and restored HER-2 and cyclin D1 protein levels. These results suggest the involvement of redox pathway also in the action of curcumin. Taken together, our data indicate multiple pathways in the mechanism of action of curcumin in HER-2 positive breast cancer cells, and suggest possible preventive strategies with this natural plant product. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5445. doi:1538-7445.AM2012-5445