Berberine Suppresses TPA-Induced Fibronectin Expression through the Inhibition of VEGF Secretion in Breast Cancer Cells

• Published in: Cellular physiology and biochemistry Vol. 32; no. 5; pp. 1541 - 1550
• Main Authors: Kim, Sangmin, Oh, Soo-Jin, Lee, Jeongmin, Han, Jeonghun, Jeon, Myeongjin, Jung, Taewoo, Lee, Se Kyung, Bae, Soo Youn, Kim, Jiyoung, Gil, Won Ho, Kim, Seok Won, Lee, Jeong Eon, Nam, Seok Jin
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Cell Physiol Biochem Press GmbH & Co KG 01.01.2013
• Subjects: AKT; Berberine; Berberine - pharmacology; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor; Female; Fibronectin; Fibronectins - metabolism; Humans; MCF-7 Cells - drug effects; Original Paper; Phosphatidylinositol 3-Kinases - metabolism; PI-3K; Proto-Oncogene Proteins c-akt - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor A - pharmacology; VEGF; Berberine; AKT; PI-3K; VEGF; Fibronectin
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000356591

Background/Aims: Berberine (BBR) is an isoquinoline alkaloid and is beneficial for the anticancer effect on a variety of human tumor cells. However, BBR's anti-angiogenesis property and its clinical potential as an inhibitor of tumor angiogenesis in breast cancer cells have not been fully elucidated. Here, we investigated the effect of BBR on TPA-induced VEGF and fibronectin (FN) as well as VEGF-induced FN in breast cancer cells. Methods: The secretion of VEGF protein was detected by ELISA. Fibronectin mRNA and protein expression was analyzed by Real-Time PCR and western blotting, respectively. The overexpressions of CA-MEK, and CA-Akt were examined by adenovirus system. Results: Our results showed that TPA, a tumor promoter, significantly increased the level of VEGF and FN expression in both MCF7 and T47D breast cancer cells. On the other hand, TPA-induced VEGF and FN expression was suppressed by LY294002, a PI-3K inhibitor. In contrast, the level of FN expression also significantly increased by constitutively active (CA)-AKT overexpression. We also found that TPA-induced VEGF and FN expression was decreased by BBR treatment. Finally, our results showed that VEGF augmented the expression of FN whereas VEGF-induced FN expression was decreased by BBR treatment. Conclusion: Taken together, we suggest that BBR may suppress TPA-induced VEGF and FN as well as VEGF-induced FN through the inhibition of the PI-3K/AKT pathway in breast cancer cells. Therefore, we suggest that BBR may be used as a candidate drug for the inhibition of angiogenesis of human breast cancer.