Induction of apoptosis by Armillaria mellea constituent armillarikin in human hepatocellular carcinoma.

Abstract:

:Armillaria mellea is a honey mushroom often used in the traditional Chinese medicine "Tianma". Currently, this medicinal mushroom is also used as a dietary supplement in numerous Western and Eastern countries. Armillarikin was isolated from A. mellea, and we previously discovered that it induced cytotoxicity in human leukemia cells. In this study, we further investigated the cytotoxicity of armillarikin against liver and intrahepatic bile duct cancer cells. Armillarikin was cytotoxic against human hepatocellular carcinoma Huh7, HA22T, and HepG2 cells based on the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and alamarBlue(®) assays. Armillarikin treatment also induced the collapse of the mitochondrial transmembrane potential of these cells. Furthermore, armillarikin-induced apoptotic cell death was demonstrated by sub-G1 chromosomal DNA formation by using flow cytometry. In addition, the apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-fmk. Immunoblotting also revealed the armillarikin-induced activation of procaspase-3, -8, and -9 and upregulation of the apoptosis- and cell cycle arrest-related phospho-histones 2 and 3, respectively. Moreover, reactive oxygen species scavengers also inhibited the armillarikin-induced apoptosis in human hepatocellular carcinoma, suggesting that reactive oxygen species formation played an important role in the armillarikin-induced apoptosis of human hepatocellular carcinoma. In conclusion, our study indicates the potential of armillarikin as an effective agent for hepatoma or leukemia therapies.

journal_name

Onco Targets Ther

journal_title

OncoTargets and therapy

authors

Chen YJ,Chen CC,Huang HL

doi

10.2147/OTT.S103940

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

4773-83

issn

1178-6930

pii

ott-9-4773

journal_volume

9

pub_type

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