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Evidence-Based Complementary and Alternative Medicine
Volume 2012 (2012), Article ID 486568, 12 pages
http://dx.doi.org/10.1155/2012/486568
Research Article

The Potential Utility of Curcumin in the Treatment of HER-2-Overexpressed Breast Cancer: An In Vitro and In Vivo Comparison Study with Herceptin

1Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua 50006, Taiwan
2Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
3Department of Pharmacology, Changhua Christian Hospital, Changhua 50006, Taiwan
4School of Medicine, College of Health Care and Management, Chung Shan Medical University, Taichung 40201, Taiwan
5School of Nutrition, College of Health Care and Management, Chung Shan Medical University, Taichung 40201, Taiwan
6Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan
7School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
8Department of Pharmacology, School of Pharmacology, China Medical University, Taichung 40402, Taiwan

Received 11 November 2010; Revised 21 March 2011; Accepted 2 May 2011

Academic Editor: Jae Youl Cho

Copyright © 2012 Hung-Wen Lai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

HER-2 is an important oncoprotein overexpressed in about 15–25% of breast cancers. We hypothesized that the ability of curcumin to downregulate HER-2 oncoprotein and inhibit the signal transduction pathway of PI3K/Akt, MAPK, and NF-κB activation may be important in the treatment of HER-2-overexpressed breast cancer. To examine the effect of curcumin on breast cancer cells, MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr (a herceptin resistant strain from SK-BR-3) cells were used for in vitro analysis. The in vivo effect of curcumin on HER-2-overexpressed breast cancer was investigated with the HER-2-overexpressed BT-474 xenograft model. Cell growth, cell cycle change, the antimobility effect, signal transduction, and xenograft volume analysis between groups treated with herceptin and/or curcumin were tested. Curcumin decreased the cell growth of various breast cancer cell lines (MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr). In Western blot analysis, the phosphorylation of Akt, MAPK, and expression of NF-κB were reduced in BT-474 cells, but not in SK-BR-3-hr cells, after treatment with herceptin. When treated with curcumin, the HER-2 oncoprotein, phosphorylation of Akt, MAPK and expression of NF-κB were decreased in both BT-474 and SK-BR-3-hr cells. In the BT-474 xenograft model, though not as much as herceptin, curcumin did effectively decrease the tumor size. The combination of curcumin with herceptin was not better than herceptin alone; however, the combination of taxol and curcumin had an antitumor effect comparable with taxol and herceptin. The results suggested that curcumin has potential as a treatment for HER-2-overexpressed breast cancer.