Growth Suppression of HER2-Overexpressing Breast Cancer Cells by Berberine via Modulation of the HER2/PI3K/Akt Signaling Pathway

• Published in: Journal of agricultural and food chemistry Vol. 59; no. 15; pp. 8216 - 8224
• Main Authors: Kuo, Han-Peng, Chuang, Tzu-Chao, Yeh, Ming-Han, Hsu, Shih-Chung, Way, Tzong-Der, Chen, Po-Yuan, Wang, Shan-Shue, Chang, Yung-Hsien, Kao, Ming-Ching, Liu, Jah-Yao
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 10.08.2011
• Subjects: anticarcinogenic activity; apoptosis; berberine; Berberine - pharmacology; Biological and medical sciences; breast neoplasms; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; caspases; cell cycle; Cell Line, Tumor; Cell Proliferation; Cell Proliferation - drug effects; Chemical Aspects of Biotechnology/Molecular Biology; cyclins; Down-Regulation; Down-Regulation - drug effects; drug effects; drug therapy; Female; Food industries; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Neoplastic - drug effects; genetics; Growth Substances; Growth Substances - pharmacology; Humans; metabolism; mitochondria; paclitaxel; pharmacology; Phosphatidylinositol 3-Kinases; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Receptor, ErbB-2; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; signal transduction; Signal Transduction - drug effects; PI3K/Akt signaling cascade; breast cancer; apoptosis; HER2; cell cycle arrest; berberine; Growth; Suppression; Malignant tumor; Cell; Cycle; Cancer
• ISSN: 0021-8561; 1520-5118; 1520-5118
• DOI: 10.1021/jf2012584

Berberine (BBR) is a natural alkaloid with significant antitumor activities against many types of cancer cells. This study investigated the molecular mechanisms by which BBR suppresses the growth of HER2-overexpressing breast cancer cells. The results show that BBR induces G1-phase cell cycle arrest by interfering with the expression of cyclins D1 and E and that it induces cellular apoptosis through the induction of a mitochondria/caspase pathway. The data also indicate that BBR inhibits cellular growth and promotes apoptosis by down-regulating the HER2/PI3K/Akt signaling pathway. Furthermore, it is also shown that a combination of taxol and BBR significantly slows the growth rate of HER2-overexpressing breast cancer cells. In conclusion, this study suggests that BBR could be a useful adjuvant therapeutic agent in the treatment of HER2-overexpressing breast cancer.