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

Breast Cancer: Basic and Clinical Research

Original Research

Rita Nahta¹  Danica L. Rowe²  Tuba Ozbay²  Ruth M. O'Regan³ 

[1] Departments of Pharmacology, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine, Atlanta, GA 30322.;Hematology and Medical Oncology, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine, Atlanta, GA 30322.;Departments of Pharmacology, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine, Atlanta, GA 30322.;Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine, Atlanta, GA 30322.;Departments of Pharmacology, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine, Atlanta, GA 30322.;Winship Cancer Institute, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine, Atlanta, GA 30322.;Hematology and Medical Oncology, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine, Atlanta, GA 30322.;Winship Cancer Institute, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine, Atlanta, GA 30322.;

关键词: mammary carcinoma;    triple negative;    curcumin;    DNA damage;    BRCA1;   

DOI  :  10.4137/BCBCR.S3067

来源: Sage Journals

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2009 SAGE Publications.

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