Abstract 1892: Curcumin induces apoptosis in H-Ras transformed human mammary epithelial cells: Cysteine 259 of STAT3 as a putative target

Abstract

Abstract Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is latent but constitutively activated in many types of cancers. It is well known that STAT3 plays a key role in inflammation-associated tumorigenesis. Curcumin, a natural compound isolated from the traditional Indian spice turmeric (Curcuma longa.,Zingiberaceae), has anti-tumor, anti-proliferative and anti-inflammatory properties. This compound has been extensively used in traditional herbal medicine over the centuries mainly due to its pronounced anti-inflammatory effects. Many studies suggest that curcumin regulates various cancer-related intracellular signaling pathways without damaging normal cells and tissues. Here, we report that curcumin effectively inhibits activation of STAT3 in dose- and time-dependent manners and causes apoptosis of H-Ras transformed breast epithelial cells (H-Ras MCF10A). Specific cysteine residues present in STAT3 appear to be critical for the activity as well as conformation of this transcription factor. We identified the cysteine residue 259 as a putative target of curcumin. We found that the α,β-unsaturated carbonyl moiety of curcumin appears to be essential in its direct binding to STAT3. Tetrahydrocurcumin that lacks the electrophilic α,β-unsaturated carbonyl moiety failed to inhibit STAT3 activation and to induce apoptosis in the same cell line. Taken together, our findings suggest that curcumin can abrogate persistently activated STAT3 signaling through direct interaction, thereby inhibiting STAT3-mediated mammary carcinogenesis. Citation Format: Young-Il Hahn, Su-Jung Kim, Bu-Young Choi, Hye-Kyung Na, Young-Joon Surh. Curcumin induces apoptosis in H-Ras transformed human mammary epithelial cells: Cysteine 259 of STAT3 as a putative target. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1892. doi:10.1158/1538-7445.AM2015-1892