Berberine suppresses TPA-induced fibronectin expression through the inhibition of VEGF secretion in breast cancer cells.

Abstract

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.

• Authors: Sangmin Kim, Soo-Jin Oh, Jeongmin Lee, Jeonghun Han, Myeongjin Jeon, Taewoo Jung, Se Kyung Lee, Soo Youn Bae, Jiyoung Kim, Won Ho Gil, Seok Won Kim, Jeong Eon Lee, Seok Jin Nam
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 32 Issue 5 Pg. 1541-50 ( 2013) ISSN: 1421-9778 [Electronic] Germany
• PMID: 24335179 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 S. Karger AG, Basel.

Chemical References

• Fibronectins
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Berberine
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Tetradecanoylphorbol Acetate

Topics

• Berberine (pharmacology)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Female
• Fibronectins (metabolism)
• Humans
• MCF-7 Cells (drug effects)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Tetradecanoylphorbol Acetate (pharmacology)
• Vascular Endothelial Growth Factor A (metabolism, pharmacology)