Rosmarinic Acid Induces Proliferation Suppression of Hepatoma Cells Associated with NF-κB Signaling Pathway

Abstract

Background: Rosmarinic acid (RA) is a natural phenolic compound that acts as a Fyn inhibitor by 53 homology modeling of the human Fyn structure. Therefore, the apoptosis mechanism related to NF-κB signaling pathway induced by RA in HepG2 was investigated. Methods: The cell growth, apoptosis, and proliferation of HepG2 regulated by various concentrations of RA were studied. The proteins expression of MMP-2, MMP-9, PI3K, AKT, NF-κB, and apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3 were detected. Results: RA significantly reduced proliferation rates, inhibited migration and invasion, and decreased the expressions of invasion-related factors, such as matrix metalloproteinase (MMP)-2 and MMP-9. TUNEL staining revealed that RA resulted in a dose-dependent increase of HepG2 cell apoptosis. In line with this finding, the expression of apoptosis suppressor protein Bcl-2 was downregulated and that of the pro-apoptotic proteins Bax and cleaved caspase-3 was increased. In addition, we found that the phosphatidylinositol 3-kinase (PI3K)/Akt/nuclear factor kappa B (NF-κB) signaling pathway was involved in RA-mediated inhibition of HepG2 cell metastasis. Conclusion: Our study identified that RA as a drug candidate for the treatment of HCC.

Suppressive Effects of Rosmarinic Acid Rich Fraction from Perilla on Oxidative Stress, Inflammation and Metastasis Ability in A549 Cells Exposed to PM via C-Jun, P-65-Nf-Κb and Akt Signaling Pathways

“…Other reports showed that the perilla extract rich in RA [74] and RA compounds had a considerable inhibitory effect on inflammation via suppression of the NF-κB signaling pathway during both in vitro and in vivo experiments [103,104]. Moreover, RA inhibited the invasion and migration of human glioma cells [85] and human hepatoma cells through the PI3K/Akt/NF-κB signaling pathway [105].…”