Modulation of the BRCA1 Protein and Induction of Apoptosis in Triple Negative Breast Cancer Cell Lines by the Polyphenolic Compound Curcumin

• Type of Material: Article
• Authors: Danica L. Rowe, Emory University; Tuba Ozbay, Emory University; Ruth O'Regan, Emory University; Rita Nahta, Emory University
• Language: English
• Date: 2009
• Publisher: Libertas Academica
• Publication Version: Final Published Version
• Copyright Statement: © the authors, licensee Libertas Academica Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://www.la-press.com/modulation-of-the-brca1-protein-and-induction-of-apoptosis-in-triple-n-article-a1623
• Title of Journal or Parent Work: Breast Cancer: Basic and Clinical Research
• ISSN: 1178-2234
• Volume: 3
• Start Page: 61
• End Page: 75
• Grant/Funding Information: Grant Support is acknowledged from National Cancer Institute K01CA118174, Georgia Cancer Coalition Distinguished Cancer Scholar Award, and Emory University Research Committee Grant to R. Nahta.
• Keywords: curcumin; DNA damage; triple negative; mammary carcinoma; BRCA1
• Research Categories: Health Sciences, Oncology; Health Sciences, Pharmacology

Abstract

In the current study, we sought to examine the effects of curcumin in a specific type of breast cancer called triple negative breast cancer. These cancers lack expression of the estrogen and progesterone receptors and do not over-express HER2. Current treatment for triple negative breast cancers is limited to cytotoxic chemotherapy, and upon relapse, there are not any therapies currently available. We demonstrate here that the bioactive food compound curcumin induces DNA damage in triple negative breast cancer cells in association with phosphorylation, increased expression, and cytoplasmic retention of the BRCA1 protein. In addition, curcumin promotes apoptosis and prevents anchorage-independent growth and migration of triple negative breast cancer cells. Apoptosis and BRCA1 modulation were not observed in non-transformed mammary epithelial cells, suggesting curcumin may have limited non-specific toxicity. This study suggests that curcumin and potentially curcumin analogues should be tested further in the context of triple negative breast cancer. These results are novel, having never been previously reported, and suggest that curcumin could provide a novel, non-toxic therapy, which could lead to improved survival for patients with triple negative breast cancer. Curcumin should be studied further in this subset of breast cancer patients, for whom treatment options are severely limited.