Hesperetin Inhibits TGF-ß1-Induced Migration and Invasion of Triple Negative Breast Cancer MDA-MB-231 Cells via Suppressing Fyn/Paxillin/RhoA Pathway.

Triple-negative breast cancer is an aggressive subtype of breast cancer with poor clinical outcomes and poor prognosis. Hesperetin is an active component extracted from Citrus fruits and Traditional Chinese Medicine has a wide range of pharmacological effects. Here, we assessed the anti-migration and anti-invasive effects and explored inhibitory mechanisms of hesperetin on metastasis of human triple negative breast cancer MDA-MB-231 cells. Cell viability experiments revealed that 200 µM hesperetin has a clear inhibitory effect on MDA-MB-231 cells. TGF-ß1 treatment induces apparent tumor progression in MDA-MB-231 cells including aberrant wound-healing and invasion ability, which is effectively suppressed by hesperetin co-treatment. Additionally, hesperetin inhibited the TGF-ß1-mediated actin stress fiber formation. Western blot results showed that hesperetin suppressed the TGF-ß1-mediated (i) activation of Fyn, (ii) phosphorylation of paxillin at Y31, Y88, and Y118 sites, (iii) the increased expression of RhoA, and (iv) activation of Rho-kinase. We demonstrated the increased interaction of Fyn with paxillin and RhoA protein in the TGF-ß1-induced metastasis of MDA-MB-231 cells. Small interfering RNA Fyn inhibited phosphorylation of paxillin (Y31) and activation of Rho-kinase induced by TGF-ß1. In conclusion, hesperetin has a significant inhibitory effect on migration and invasion of MDA-MB-231 cells induced by TGF-ß1, which might be attributed to inhibiting the Fyn/paxillin/RhoA pathway.

Downregulated lncRNA SNHG18 Suppresses the Progression of Hepatitis B Virus-Associated Hepatocellular Carcinoma and Meditates the Antitumor Effect of Oleanolic Acid.

PURPOSE: Oleanolic acid (OA) has been widely reported to possess antitumor effects, but the specific molecular mechanism underlying its inhibition of hepatocellular carcinoma (HCC) progression remains unclear. This study aims to uncover the mechanism of OA antitumor effect on HBV-associated HCC and identify a potential biomarker for tumor progression. PATIENTS AND METHODS: The effect of OA on major cellular processes of HBV-associated HCC cells was evaluated by CCK8 and Transwell assay. The potential molecular mechanism was assessed by cell transfection. This study also enrolled 111 HCC patients infected with HBV to evaluate the prognostic potential of lncRNA SNHG18 (SNHG18) in HBV-associated HCC. RESULTS: The inhibitory effect of OA was observed in the critical cellular processes of HBV-associated HCC cells, which depend on OA concentration. Downregulated SNHG18 in HBV-associated HCC was demonstrated to be involved in disease development and predict patients' prognosis. The downregulation of SNHG18 dramatically promoted cellular processes of HBV-associated HCC could reverse the inhibitory effect of OA. CONCLUSION: SNHG18 served as a tumor suppressor and prognostic biomarker of HBV-associated HCC. Enhancing SNHG18 might be the mechanism underlying the antitumor effect of OA in HBV-associated HCC.