Ursolic Acid Attenuates TGF-β1-Induced Epithelial‐Mesenchymal Transition in NSCLC by Targeting Integrin αVβ5/MMPs Signaling

Abstract

Transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) of non-small-cell carcinoma (NSCLC) may contribute to tumor metastasis. TGF-β1-induced EMT in H1975 cells (a human NSCLC cell line) resulted in the adoption of mesenchymal responses that were predominantly mediated via the TGF-β1-integrin signaling pathway. Ursolic acid has been previously reported to inhibit tumor growth and metastasis in several cancers. However, whether ursolic acid can attenuate TGF-β1-induced EMT in H1975 cells and its underlying mechanisms remains unknown. In this study, ursolic acid significantly attenuated the TGF-β1-induced decrease in E-cadherin level and elevated the level of N-cadherin. Furthermore, ursolic acid inhibited the mesenchymal-like responses in H1975 cells, including cell migration, invasion and activity of matrix metallopeptidase (MMP)-2 and -9. Finally, our new findings provided evidence that, ursolic acid could inhibit EMT in NSCLC through TGF-β1 signaling pathway mediated integrinαVβ5 expression, and this might the potential mechanism of resveratrol on the inhibition of invasion and metastases in NSCLC. We conclude that ursolic acid attenuated TGF-β1-induced EMT in H1975 cells and might be a promising therapeutic agent for treating NSCLC.

Ursolic Acid Inhibits Tumor Growth <i>via</i> Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells

“…UA shows a variety of biological effects that are likely to influence cancer development, including antiviral, anti-inflammatory, antioxidant, hepatoprotective, anti-tumor, cytotoxic, anti-metastatic activities, and anti-angiogenetic. [15][16][17] UA inhibits the metastasis of colorectal cancer by suppressing multiple biomarkers associated to invasion, angiogenesis, and metastasis. 4) A recent study demonstrated that UA could inhibit EMT in nonsmall-cell lung cancer (NSCLC) through transforming growth factor-β (TGF-β)1 signaling pathway, and this might be the potential mechanism of resveratrol on the inhibition of invasion and metastases in NSCLC.…”

“…4) A recent study demonstrated that UA could inhibit EMT in nonsmall-cell lung cancer (NSCLC) through transforming growth factor-β (TGF-β)1 signaling pathway, and this might be the potential mechanism of resveratrol on the inhibition of invasion and metastases in NSCLC. 18) However, no reports has showed on its role in EMT mediated metastasis in colorectal cancer. Therefore, we demonstrate that UA inhibits the growth and metastasis of colorectal cancer cells by affecting targets that promote EMT.…”

Vimentin Intermediate Filaments as Potential Target for Cancer Treatment

“…Silibin, resveratrol, and dioscin all suppress vimentin expression and decrease migration and invasion [102,108,112,113]. Ursolic acid has these effects and also reduces tumor cell growth and induces apoptosis [116,127]. In a similar fashion, a component of ginseng, Ginsenoside 20(R)-Rg3, has been found to prevent EMT upon TGF-β stimulation, repressing vimentin among other EMT markers [105].…”

Intermediate Filaments as Potential Target for Cancer 2 Treatment

“…Silibin, resveratrol, and dioscin all suppress vimentin expression and decrease migration and invasion [110][111][112][113]. Ursolic acid has these effects and also reduces tumor cell growth and induces apoptosis [114,115]. In a similar fashion, a component of ginseng, Ginsenoside 20(R)-Rg3, has been found to prevent EMT upon TGF-β stimulation, repressing vimentin among other EMT markers [116].…”