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Molecules 2013, 18(1), 701-720; doi:10.3390/molecules18010701
Article

Curcumin Induces Cell Death and Restores Tamoxifen Sensitivity in the Antiestrogen-Resistant Breast Cancer Cell Lines MCF-7/LCC2 and MCF-7/LCC9

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, 1
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, 2,*  and 1,*
1 Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 2 Division of Antitumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
* Authors to whom correspondence should be addressed.
Received: 2 November 2012 / Revised: 24 December 2012 / Accepted: 26 December 2012 / Published: 8 January 2013
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Abstract

Curcumin, a principal component of turmeric (Curcuma longa), has potential therapeutic activities against breast cancer through multiple signaling pathways. Increasing evidence indicates that curcumin reverses chemo-resistance and sensitizes cancer cells to chemotherapy and targeted therapy in breast cancer. To date, few studies have explored its potential antiproliferation effects and resistance reversal in antiestrogen-resistant breast cancer. In this study, we therefore investigated the efficacy of curcumin alone and in combination with tamoxifen in the established antiestrogen-resistant breast cancer cell lines MCF-7/LCC2 and MCF-7/LCC9. We discovered that curcumin treatment displayed anti-proliferative and pro-apoptotic activities and induced cell cycle arrest at G2/M phase. Of note, the combination of curcumin and tamoxifen resulted in a synergistic survival inhibition in MCF-7/LCC2 and MCF-7/LCC9 cells. Moreover, we found that curcumin targeted multiple signals involved in growth maintenance and resistance acquisition in endocrine resistant cells. In our cell models, curcumin could suppress expression of pro-growth and anti-apoptosis molecules, induce inactivation of NF-κB, Src and Akt/mTOR pathways and downregulate the key epigenetic modifier EZH2. The above findings suggested that curcumin alone and combinations of curcumin with endocrine therapy may be of therapeutic benefit for endocrine-resistant breast cancer.
Keywords: curcumin; endocrine resistance; tamoxifen; NF-κB; Src/FAK; Akt/mTOR; EZH2; cyclin D1; c-Myc curcumin; endocrine resistance; tamoxifen; NF-κB; Src/FAK; Akt/mTOR; EZH2; cyclin D1; c-Myc
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.

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MDPI and ACS Style

Jiang, M.; Huang, O.; Zhang, X.; Xie, Z.; Shen, A.; Liu, H.; Geng, M.; Shen, K. Curcumin Induces Cell Death and Restores Tamoxifen Sensitivity in the Antiestrogen-Resistant Breast Cancer Cell Lines MCF-7/LCC2 and MCF-7/LCC9. Molecules 2013, 18, 701-720.

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