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.

Berberine suppresses Id-1 expression and inhibits the growth and development of lung metastases in hepatocellular carcinoma

“…On the other hand, chemotherapy is commonly applied for inoperable HCC, but its results are often discouraging because of chemoresistance conferred by p53 mutation in HCC cells and toxicity of chemotherapeutic agents to normal cells [28]. The potent anti-tumor effects of berberine has been reported in multiple cancer types [2,6,8,9]. In agreement with other published reports showing the anti-cancer effects of berberine, we have also demonstrated the inhibitory effects of berberine on the growth of HCC in vivo (Fig.…”

“…Coptis Rhizome has been used for centuries by Chinese medicine physician for the treatment of cancer and inflammatory diseases [2]. Berberine is known to possess potent anti-cancer activity in several cancer models including, breast, gastric and colon cancers, nasopharyngeal carcinoma (NPC) as well as HCC [3][4][5][6][7][8]. The anti-tumor activity of berberine includes the induction of cancer cell apoptosis through affecting the normal mitochondria functioning [5,8], anti-angiogenesis by destabilizing of HIF-1α protein in hypoxic gastric adenocarinoma cells [7], and suppressing of VEGF secretion in breast and gastric cancer cells [6,7].…”

“…Berberine is known to possess potent anti-cancer activity in several cancer models including, breast, gastric and colon cancers, nasopharyngeal carcinoma (NPC) as well as HCC [3][4][5][6][7][8]. The anti-tumor activity of berberine includes the induction of cancer cell apoptosis through affecting the normal mitochondria functioning [5,8], anti-angiogenesis by destabilizing of HIF-1α protein in hypoxic gastric adenocarinoma cells [7], and suppressing of VEGF secretion in breast and gastric cancer cells [6,7]. Our recent studies of berberine's anti-cancer action also revealed that it can inhibit STAT3 activation which is signaled by tumorassociated fibroblasts [9] and inactivate RhoGTPases to interrupt cytoskeletal dynamics and cell mobility in NPC [3].…”

Berberine Suppresses Cell Motility Through Downregulation of TGF-β1 in Triple Negative Breast Cancer Cells

“…In particular, low-dose treatment (≤ 20 mM) with BBR induces G1/S arrest, while high-dose treatment (50 mM) with BBR inhibits the G2/M checkpoint in RM-1 prostate cancer cells [32]. BBR also inhibits tumor cell invasion and angiogenesis, which in turn suppresses cancer metastasis, by suppression of MMP-2, MMP-9, and VEGF [23, 33, 34]. Consistent with previous studies, we show that BBR induces arrest in the G0/G1 phase and inhibits anchorage-independent growth in MDA-MB231 breast cancer cells.…”

Induction of fibronectin by HER2 overexpression triggers adhesion and invasion of breast cancer cells

“…Heparin-binding EGF-like growth factor (HB-EGF) is an intermediate molecule for TGF-β-mediated EGFR transactivation, which subsequently triggers the transcriptional activity of FN via activation of ERK and p38MAPK in glomerular mesangial cells [27]. Moreover, vascular endothelial growth factor (VEGF) also augments FN expression in breast cancer cells via the PI-3K/Akt-dependent pathway [29]. In the present study, we found that induction of FN by HER2 activation decreased in response to treatment with UO126 (a MEK 1/2 inhibitor), LY294002 (a PI-3K inhibitor), and Stattic (a STAT3 inhibitor), in SKBR3 cells.…”