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Background: Xanthomicrol is one of the methoxylated flavones and a promising cancer chemopreventive agent, but its anti-migration and anti-invasion ability on human hepatocellular carcinoma (HCC) remains unknown. Objectives: This study aims to explore Xanthomicrol's effects on migration and invasion ability of the human HCC Huh7 cell line. Methods: Viability of Huh7 cells was measured by cell counting kit-8 (CCK8) assay. Cell apoptosis was assayed with flow cytometry analysis. The ability of migration and invasion of Huh7 cells was then detected through Transwell assays. Epithelial–mesenchymal transition (EMT)-related proteins were also detected through Western blot. Key findings: Xanthomicrol inhibits the migration and invasion of Huh7 cells. The overexpression of Μu-opioid receptor (MOR) increases Huh7 cells' proliferation and enhances migration and invasion ability, while xanthomicrol treatment decreases the expression of MOR. Moreover, xanthomicrol can reverse migration, invasion and EMT-related protein expression by overexpressed MOR. Conclusions: These results suggest that xanthomicrol is a potential MOR antagonist, and it possesses potent anti-migration and anti-invasion ability on Huh7 cells. [ABSTRACT FROM AUTHOR]

Objectives: Eurycoma longifolia Jack (Simaroubaceae) is commonly distributed in the Southeast Asia and Indo China, which has been shown to possess antianxiety, antibacterial, anticancer, antifungal, anti‐inflammatory, antimalarial and antioxidant biological activities. 14,15β‐dihydroxyklaineanone is a diterpene isolated from E. longifolia Jack, which is cytotoxic against human lung cancer and human breast cancer cell lines. However, the effects and underlying mechanisms of 14,15β‐dihydroxyklaineanone on hepatocellular carcinoma remain unknown. Methods: Cell viability assay and colony formation assay were used to measure HepG2 cell proliferation. Flow cytometry was used to analyse cell cycle and apoptosis. Wound‐healing assay and transwell assay were used to observe cells migration. RNA sequencing and the enrichment of differentially expressed genes (DEGs) in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used to find and determine underlying pathways. Key findings: We found that 14,15β‐dihydroxyklaineanone inhibited the growth and migration of HepG2 cells but did not induce cell apoptosis. 14,15β‐dihydroxyklaineanone induced S cell cycle arrest by downregulating the expression levels of cyclin A, p‐CDK2, cyclin B1, p21, E2F‐1 and PCNA. In addition, RNA sequencing showed that 14,15β‐dihydroxyklaineanone regulated MAPK pathway by increasing the expression levels of phosphor‐p38. Downregulating of p38 via both p38 inhibitor (SB203580) and p38‐siRNA could antagonize the inhibition of cell proliferation and migration and reverse the changes in p‐p38, E‐cadherin, N‐cadherin and PCNA expression induced by 14,15β‐dihydroxyklaineanone treatment. Conclusions: 14,15β‐dihydroxyklaineanone inhibited cell proliferation and migration through regulating p38 MAPK pathway in HCC cells. [ABSTRACT FROM AUTHOR]