Effect of Alkylresorcinols on Autophagy, Migration, and Invasion of HepG2 Cells

Abstract

Alkylresorcinols are phenolic lipids that mainly exist in the cortex of grains, and they exhibit anticancer activity against various cancer cells in vitro. However, the underlying action mechanisms are still unclear. In our study, the influence of alkylresorcinols C19:0 and C21:0 (ARs) upon migration, invasion, and autophagy in human hepatoblastoma HepG2 cells was evaluated. Results showed that ARs at 80 and 160 µg/mL significantly suppressed cells proliferation, migration, and invasion, downregulated the expression of proteins RhoA and MMP‐7 associated with migration and invasion. ARs at 160 µg/mL, the rate of LC3 puncta was appreciably increased. After autophagy was blocked by 3‐MA or CQ, the expression of LC3II was significantly increased in 3‐MA+ARs group and p62 was significantly decreased in CQ+ARs group. The results indicate that ARs may promote autophagic flow. ARs (80, 160 µg/mL) significantly inhibited the expression of proteins p‐mTOR, p‐PI3K, and p‐Akt related to the PI3K/Akt pathway. The results of the present study suggest that ARs can activate autophagy and suppresses the biological behaviors of HepG2 cells by inhibiting the activation of MMP‐7, Rho/Rho‐associated protein kinase, and activation of the phosphatidylinositol 3‐kinase/Akt signaling pathway. Practical Application The anticancer mechanism of ARs in wheat bran was studied, which provided a basis for the development of anticancer functional auxiliary food with wheat bran as raw material. It is of great practical significance to promote the effective utilization of grain processing by‐products and improve the economic benefits of the grain industry.

Apple polyphenol extract alleviates lipid accumulation in free‐fatty‐acid‐exposed HepG2 cells via activating autophagy mediated by SIRT1/AMPK signaling

“…To verify our speculation, also considering HAP treatment had a more obvious promoting‐autophagy effect, we selected HepG2 cells in high dose of APE treatment group being treated with autophagy blockers, CQ and leupeptin, respectively. Consistent with Guo' study (Guo, Yang, & Li, 2019), elevated protein accumulations of LC3‐II and p62 were observed in CQ‐treated HepG2, and LC3‐II protein accumulation was more obvious in APE treatment group. Similar phenomena were also observed in leupeptin‐treated cells.…”

Analysis of the multi-physiological and functional mechanism of wheat alkylresorcinols based on reverse molecular docking and network pharmacology

“…48,49 One study found that the knockdown of HSP90 blocked AKT1 phosphorylation. 64 However, Ars and AR-C17 treatment also decreases p-AKT in some cancer cells (HepG2 cells and MCF-7 breast cancer cells), 47,48 and whether this is related to the inhibition of HSP90 by ARs or its metabolites needs to be further verified. EP300 (E1A-associated protein p300) is a pleiotropic multidomain coactivator that acts as a histone/lysine acetyl transferase, chromatin remodeler, and acetyltransferase for nonhistone targets.…”

“…48,49 One study found that the knockdown of HSP90 blocked AKT1 phosphorylation. 64 However, Ars and AR-C17 treatment also decreases p-AKT in some cancer cells (HepG2 cells and MCF-7 breast cancer cells), 47,48 and whether this is related to the inhibition of HSP90 by ARs or its metabolites needs to be further verified.…”

“…7B, it was found that there were many KEGG pathways involved in RXRB, RXRG, HSP90AB1, MAPK14, HSP90AA1, PPARG, JAK2, and MMP9. It has been reported that the physiological anticancer function of ARs may be related to the PI3K/Akt signaling pathway, 47,48 p53 pathway, 49 promote LC3-II expression, 50 and inhibit the activity of CYP17A1. 46 Regulation of oxidative stress is also one of the important physiological functions of ARs, which is related to Akt-dependent Nrf2/HO-1 19 and Nrf2/ARE pathways, 21 SIRT3/FOXO3a signaling pathway, 22 and SIRT3/ SOD2 signaling pathway.…”

Germacrone Regulates HBXIP-Mediated Cell Cycle, Apoptosis and Promotes the Formation of Autophagosomes to Inhibit the Proliferation of Gastric Cancer Cells

“…The expression of LC3II and LC3II/LC3I also increased rapidly in gastric cancer cells treated with germacrone ( Figures 4B, C). Baf A1 is an autophagy inhibitor, which affects the binding of autophagosomes to lysosomes, and the increasing of LC3 (24,25). In our study, we used Baf A1 to investigate the regulatory target of germacrone on autophagy.…”