Asperolide A induces apoptosis and cell cycle arrest of human hepatoma cells with p53-Y220C mutant through p38 mediating phosphorylation of p53 (S33)

Asperolides A (AA), one of the new tetranorlabdane diterpenoids, is proved to inhibit the proliferation of lung cancer cells and bone metastasis of breast cancer cells. Herein, we report that AA induces apoptosis and cell cycle arrest of hepatoma cells. It intensely inhibits proliferation of Huh-7 c...

Full description

Saved in:
Bibliographic Details
Published in:Heliyon 2023-03, Vol.9 (3), p.e13843-e13843, Article e13843
Main Authors: Lv, Cuiting, Lan, Aihua, Fan, Xiao, Huang, Caiguo, Yang, Gong
Format: Article
Language:English
Subjects:
Apoptosis
Asperolide A
breast neoplasms
Cell cycle arrest
cell cycle checkpoints
cell viability
diterpenoids
drugs
hepatoma
Hepatoma cell
humans
lung neoplasms
MAPK
metastasis
mitogen-activated protein kinase
mutants
p53 mutation
phosphorylation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Asperolides A (AA), one of the new tetranorlabdane diterpenoids, is proved to inhibit the proliferation of lung cancer cells and bone metastasis of breast cancer cells. Herein, we report that AA induces apoptosis and cell cycle arrest of hepatoma cells. It intensely inhibits proliferation of Huh-7 cell, compared with HepG-2 and L02 cells. AA elevates the activity of mitogen-activated protein kinases (MAPKs), in which the activation of ERK and JNK improves cell survival. However, phosphorylation of p53 at S33 by p38 activation could be a principal factor in the AA-induced apoptosis and G2/M cell cycle arrest of Huh-7 cells. The S33 site of p53-Y220C mutant, as the specific activation site of p38, reactivates the wild-type function of mutant p53 protein, which leads to a higher sensitivity of Huh-7 cells to AA. These results provide new insights into the molecular mechanisms of AA as a developing mutant p53 rescue drug.
ISSN:2405-8440
2405-8440
DOI:10.1016/j.heliyon.2023.e13843