Open Access14,15β‐dihydroxyklaineanone inhibits HepG2 cell proliferation and migration through p38MAPK pathway
Author(s) -
Pei XiaoDong,
He SongQing,
Shen LiQun,
Wei JingChen,
Li XueSheng,
Wei YanYan,
Zhang YuMeng,
Wang XinYu,
Lin Feng,
He ZhiLong,
Jiang LiHe
Publication year - 2020
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.13289
Subject(s) - cell growth , cell cycle , biology , viability assay , cyclin b1 , cyclin a , cyclin d1 , mtt assay , kegg , microbiology and biotechnology , cell cycle checkpoint , cell migration , apoptosis , mapk/erk pathway , cell , signal transduction , cyclin dependent kinase 1 , gene expression , biochemistry , gene , transcriptome
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.