Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Oncogene, 2010-01, Vol.29 (2), p.285-296

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 G 0 /G 1 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 p27 KIP1 , 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.