Abstract B65: Curcumin, a novel inhibitor of ATR-CHK1 pathway, suppresses homologous recombination and DNA damage checkpoint and enhances the sensitivity to PARP inhibitors.

Abstract

Abstract Curcumin is a major chemical component of turmeric (curcuma longa) and is used as a spice to give a specific flavor and yellow color in Asian foods. Here we show that treatment of (HeLa) cells with curcumin suppresses DNA damage checkpoint response and homologous recombination repair (HRR). Curcumin inhibited the phospohrylation of CHK1, but not of ATM and CHK2, induced by DNA damage. Furthermore, cells treated with curcumin failed to form ionizing radiation (IR), hydroxyurea (HU) or camptothecin (CPT)-induced RAD51 foci, but not RPA32, 53BP1 and BRCA1 foci. These results suggested that curcumin suppressed HRR and DNA damage checkpoint response through inhibition of the ATR-CHK1 pathway. In fact, curcumin led to accumulate DSBs and increase the apoptotic and necrotic cell death induced by a poly(ADP-ribose polymerase (PARP) inhibitor. It was noted that curcumin enhanced the sensitivity of cancer cells to the PARP inhibitor, which is a promising anti-cancer drug that selectively kills cells deficient for DNA damage response (DDR) including HRR and DNA damage checkpoint response. Taken together, combination of the PARP inhibitor with curcumin was indicated to have a potential to enhance the efficacy of PARP inhibitor-based cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B65.