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Capsaicin causes cell-cycle arrest and apoptosis in ER-positive and -negative breast cancer cells by modulating the EGFR/HER-2 pathway

Oncogene volume 29, pages 285–296 (2010)Cite this article

Abstract

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is an ingredient of chili peppers with inhibitory effects against cancer cells of different origin. We examined the activity of capsaicin on breast cancer cells in vitro and in vivo. The drug potently inhibited growth of ER-positive (MCF-7, T47D, BT-474) and ER-negative (SKBR-3, MDA-MB231) breast cancer cell lines, which was associated with G0/G1 cell-cycle arrest, increased levels of apoptosis and reduced protein expression of human epidermal growth factor receptor (EGFR), HER-2, activated extracellular-regulated kinase (ERK) and cyclin D1. In contrast, cell-cycle regulator p27KIP1, caspase activity as well as poly-ADP ribose polymerase (PARP) cleavage were increased. Notably, capsaicin blocked breast cancer cell migration in vitro and decreased by 50% the size of MDA-MB231 breast cancer tumors growing orthotopically in immunodeficient mice without noticeable drug side effects. in vivo activation of ERK was clearly decreased, as well as expression of HER-2 and cyclin D1, whereas caspase activity and PARP cleavage products were increased in tumors of drug-treated mice. Besides, capsaicin potently inhibited the development of pre-neoplastic breast lesions by up to 80% without evidence of toxicity. Our data indicate that capsaicin is a novel modulator of the EGFR/HER-2 pathway in both ER-positive and -negative breast cancer cells with a potential role in the treatment and prevention of human breast cancer.

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Acknowledgements

NH Thoennissen's work was supported by the Deutsche Forschungsgemeinschaft, Bonn, Germany (TH 1438/1-1); B Karlan by the Woman Cancer Institute of Cedars-Sinai Medical Center, Los Angeles, CA, USA and GB Iwanski by the Jung-Stiftung für Wissenschaft und Forschung, Hamburg, Germany. HP Koeffler is the holder of the Mark Goodson endowed Chair in Oncology Research and is a member of the Jonsson Cancer and Molecular Biology Institute, UCLA, Los Angeles, CA, USA.

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  1. N H Thoennissen and J O'Kelly: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA

    N H Thoennissen, J O'Kelly, D Lu, G B Iwanski, D T La, S Abbassi, A Leiter & H P Koeffler

  2. Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA

    B Karlan

  3. Division of Carcinogenesis and Chemoprevention, IIT Research Institute, Chicago, IL, USA

    R Mehta

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  1. N H Thoennissen
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Correspondence to N H Thoennissen.

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Thoennissen, N., O'Kelly, J., Lu, D. et al. Capsaicin causes cell-cycle arrest and apoptosis in ER-positive and -negative breast cancer cells by modulating the EGFR/HER-2 pathway. Oncogene 29, 285–296 (2010). https://doi.org/10.1038/onc.2009.335

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