Back to Search Start Over

RETRACTED: Puerarin 6″‐O‐xyloside suppressed HCC via regulating proliferation, stemness, and apoptosis with inhibited PI3K/AKT/mTOR

Authors :
Long Li
Jun‐Dong Liu
Guo‐Dong Gao
Kai Zhang
Yu‐Wei Song
Hong‐Bo Li
Source :
Cancer Medicine, Vol 9, Iss 17, Pp 6399-6410 (2020)
Publication Year :
2020
Publisher :
Wiley, 2020.

Abstract

Abstract Puerarin 6″‐O‐xyloside is a tumor suppressive derivate of Puerarin that is recently characterized as a lysine‐specific demethylase 6B inhibitor. Here we investigated the effects of Puerarin 6″‐O‐xyloside in hepatocellular carcinoma (HCC) cell lines SMMC‐7721 and HepG2. Cell viability, proliferation, stemness, protein expression, and autophagy were tested by CCK‐8, colony formation, sphere formation, western blotting, and LC3B GFP puncta per cell, respectively. Apoptosis, CD133‐positive cells, and JC‐1‐labeled mitochondrial membrane potential were measured by flow cytometry. The effects of Puerarin 6″‐O‐xyloside in vivo were explored in HepG2 xenograft mice. Puerarin 6″‐O‐xyloside inhibited cell viability, proliferation, and stemness, and promoted apoptosis in both SMMC‐7721 and HepG2 cells. Further experiments showed promoted autophagy and decreased mitochondrial membrane potential, and decreased expression of p‐PI3K, p‐AKT, and p‐mTOR in HepG2 cells. Co‐administration of 3‐MA with Puerarin 6″‐O‐xyloside obviously augmented these effects including inhibited protein expression of p‐PI3K, p‐AKT, and p‐mTOR, and inhibited proliferation, promoted apoptosis, and decreased stemness. In HepG2 xenograft mice, 100 mg/kg/d Puerarin 6″‐O‐xyloside significantly suppressed tumor growth, stemness, and apoptosis. In conclusion, our study indicated that Puerarin 6″‐O‐xyloside decreased cell viability, proliferation, and stemness, and promoted autophagy and mitochondria‐dependent apoptosis of HCC, at least partly through inhibiting PI3K/AKT/mTOR. These results highlighted Puerarin 6″‐O‐xyloside as a promising prodrug that could inhibit both PI3K/AKT/mTOR and epigenetic demethylation.

Details

Language :
English
ISSN :
20457634
Volume :
9
Issue :
17
Database :
Directory of Open Access Journals
Journal :
Cancer Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.015fcb222464693ad6780c7b06c7faa
Document Type :
article
Full Text :
https://doi.org/10.1002/cam4.3285