Carnosic acid inhibits the growth of ER-negative human breast cancer cells and synergizes with curcumin.

Abstract

BACKGROUND:

Studies indicate that extracts and purified components, including carnosic acid, from the herb rosemary display significant growth inhibitory activity on a variety of cancers.

PURPOSE:

This paper examines the ability of rosemary/carnosic acid to inhibit the growth of human breast cancer cells and to synergize with curcumin.

MATERIALS AND METHODS:

To do this, we treated human breast cancer cells with rosemary/carnosic acid and assessed effects on cell proliferation, cell cycle distribution, gene expression patterns, activity of the purified Na/K ATPase and combinations with curcumin.

RESULTS:

Rosemary/carnosic acid potently inhibits proliferation of ER-negative human breast cancer cells and induces G1 cell cycle arrest. Further, carnosic acid is selective for MCF7 cells transfected for Her2, indicating that Her2 may function in its action. To reveal primary effects, we treated ER-negative breast cancer cells with carnosic acid for 6h. At a low dose, 5 μg/ml (15 μM), carnosic acid activated the expression of 3 genes, induced through the presence of antioxidant response elements, including genes involved in glutathione biosynthesis (CYP4F3, GCLC) and transport (SLC7A11). At a higher dose, 20 μg/ml, carnosic acid activated the expression of antioxidant (AKR1C2, TNXRD1, HMOX1) and apoptosis (GDF15, PHLDA1, DDIT3) genes and suppressed the expression of inhibitor of transcription (ID3) and cell cycle (CDKN2C) genes. Carnosic acid exhibits synergy with turmeric/curcumin. These compounds inhibited the activity of the purified Na-K-ATPase which may contribute to this synergy.

CONCLUSION:

Rosemary/carnosic acid, alone or combined with curcumin, may be useful to prevent and treat ER-negative breast cancer.

• Authors: Linda Saxe Einbond, Hsan-Au Wu, Ryota Kashiwazaki, Kan He, Marc Roller, Tao Su, Xiaomei Wang, Sarah Goldsberry
• Journal: Fitoterapia (Fitoterapia) Vol. 83 Issue 7 Pg. 1160-8 (Oct 2012) ISSN: 1873-6971 [Electronic] Netherlands
• PMID: 22828666 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Abietanes
• Antineoplastic Agents, Phytogenic
• Antioxidants
• Inhibitor of Differentiation Proteins
• Neoplasm Proteins
• Plant Extracts
• Receptors, Estrogen
• ID3 protein, human
• ERBB2 protein, human
• Receptor, ErbB-2
• Glutathione
• Curcumin
• salvin

Topics

• Abietanes (pharmacology, therapeutic use)
• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Antioxidants (metabolism)
• Apoptosis (drug effects, genetics)
• Breast Neoplasms (drug therapy, genetics, metabolism)
• Cell Cycle Checkpoints (drug effects, genetics)
• Cell Proliferation (drug effects)
• Curcuma (chemistry)
• Curcumin (pharmacology, therapeutic use)
• Drug Synergism
• Female
• Gene Expression (drug effects)
• Glutathione (genetics, metabolism)
• Humans
• Inhibitor of Differentiation Proteins (metabolism)
• MCF-7 Cells
• Neoplasm Proteins (metabolism)
• Phytotherapy
• Plant Extracts (pharmacology, therapeutic use)
• Receptor, ErbB-2 (metabolism)
• Receptors, Estrogen (metabolism)
• Rosmarinus (chemistry)