Induction of apoptosis by cinobufacini preparation through mitochondria- and Fas-mediated caspase-dependent pathways in human hepatocellular carcinoma cells

► Cinobufacini has apoptosis inducing effects on human hepatocellular carcinoma (HCC) cells. ► Cinobufacini induce apoptosis through both mitochondria- and Fas-mediated pathways. ► These findings provide an experimental evidence for cinobufacini treatment of HCC. Cinobufacini (Huachansu), an aqueous...

Full description

Saved in:
Bibliographic Details
Published in:Food and chemical toxicology 2012-02, Vol.50 (2), p.295-302
Main Authors: Qi, Fanghua, Li, Anyuan, Inagaki, Yoshinori, Xu, Huanli, Wang, Dongliang, Cui, Xiaoyan, Zhang, Li, Kokudo, Norihiro, Du, Guanhua, Tang, Wei
Format: Article
Language:English
Subjects:
Amphibian Venoms - chemistry
Amphibian Venoms - pharmacology
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Biological and medical sciences
Bufo bufo
Bufonidae - metabolism
Caspase
caspase-10
caspase-3
caspase-8
caspase-9
Caspases - metabolism
cell proliferation
Cinobufacini
cytochrome c
Fas Ligand Protein - metabolism
Fas-mediated apoptosis pathway
Gastroenterology. Liver. Pancreas. Abdomen
HCC cells
Hep G2 Cells
hepatoma
Humans
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Medicine, Chinese Traditional
membrane potential
Mitochondria - drug effects
Mitochondria - enzymology
Mitochondria-mediated apoptosis pathway
mitochondrial membrane
NAD ADP-ribosyltransferase
Oriental traditional medicine
Skin - chemistry
Skin - metabolism
therapeutics
Toxicology
Tumors
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:► Cinobufacini has apoptosis inducing effects on human hepatocellular carcinoma (HCC) cells. ► Cinobufacini induce apoptosis through both mitochondria- and Fas-mediated pathways. ► These findings provide an experimental evidence for cinobufacini treatment of HCC. Cinobufacini (Huachansu), an aqueous extract from the skins of Bufo bufo gargarizans Cantor, is a well-known traditional Chinese medicine widely used in clinical cancer therapy in China. However, the precise mechanisms induced by cinobufacini in human hepatocellular carcinoma (HCC) cells are still not very clear. The aim of present study was to investigate possible apoptotic mechanisms induced by cinobufacini in HCC cell lines HepG2 and Bel-7402. We found that cinobufacini treatment resulted in a significant decrease in cell proliferation and induced apoptotic cell death with the increase of treatment time. It indicated that cinobufacini-induced apoptosis was associated with mitochondria-mediated pathway including the loss of mitochondrial membrane potential (Δψm), the increase of Bax/Bcl-2 ratio, cytochrome c release, caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) degradation. Additionally, cinobufacini also activated Fas-mediated apoptosis pathway obviously as evident by an increase in Fas expression, and caspase-8 and caspase-10 activation. Moreover, the BH3-only protein Bid was cleaved into a truncated Bid (tBid) after cinobufacini treatment. Taken together, these data suggested cinobufacini could induce apoptosis of HCC cells through mitochondria- and Fas-mediated caspase-dependent pathways with the increase of treatment time, which might provide an experimental evidence for cinobufacini treatment of HCC.
ISSN:0278-6915
1873-6351
DOI:10.1016/j.fct.2011.10.040