Abstract 5589: An aqueous extract of Allspice (berries of Pimenta dioica) inhibits breast cancer growth through autophagy by targeting the estrogen receptor

Abstract

Abstract Background: Breast cancer (BrCa) ranks second as cause of cancer deaths in women. However, >90% of BrCa patients survive >5 years after diagnosis, thus providing an chance to prevent clinical progression and metastasis. Several chemopreventive agents are currently under investigation, however, no single agent is highly effective. Dietary agents offer an advantage for long-term, well tolerated and personalized treatment for chemoprevention. With this goal, we investigated anticancer effects of an aqueous extract of a common spice, the unripe berries of Pimenta dioica (Allspice). Methods: An aqueous exact of Allspice was prepared, lyophilized and a solution of suitable strength was tested on several BrCa cell lines (MCF-7, MDA-MB231, SKBr3) for potential inhibition of clonogenic growth, autophagy and estrogen-receptor inactivation using commonly used analytical techniques. Potential effect on estrogen receptor (ERα) levels and transcriptional activities were determined using quantitative-real time PCR and western blotting. Results: AAE reduced the viability and clonogenic growth of BrCa cells (IC50≈ 100μg/ml). Importantly, AAE was selectively effective against proliferating cells but not quiescent cells. In addition to cytotoxicity, AAE reduced ERα in an estrogen-dependent BrCa cell line, MCF-7. ERα protein levels were significantly decreased in AAE treated MCF7 cells (IC50≈ 100μg/ml). The decrease in ERα protein level by AAE was not rescued by MG132, a proteasome inhibitor, treatment indicating, it is likely due to AAE effect on ERα synthesis and not turnover. We did not detect AAE induced apoptosis in MCF-7 cells as confirmed by several assays. However AAE induced the expressions of autophagy-related proteins, microtubule-associated protein 1 light chain 3 (LC3). Conclusion: We demonstrate anti-proliferative and anti-ERα activity of the aqueous extract of Allspice, a highly aromatic and delectable culinary additive world over. The cytotoxicity of this anticancer agent encompassed multiple pathways, including autophagy and ERα down modulation. These results, if found corroborative using studies in vivo models, should provide a strong rationale to test as an anti-cancer agent in breast cancer. [Grant Support: 1R01AT003544 (BLL)] Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5589. doi:10.1158/1538-7445.AM2011-5589