Apoptosis induction of human bladder cancer cells by sanguinarine through reactive oxygen species-mediated up-regulation of early growth response gene-1

Although the effects of sanguinarine, a benzophenanthridine alkaloid, on the inhibition of some kinds of cancer cell growth have been established, the underlying mechanisms are not completely understood. This study investigated possible mechanisms by which sanguinarine exerts its anticancer action i...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2013-05, Vol.8 (5), p.e63425
Main Authors: Han, Min Ho, Park, Cheol, Jin, Cheng-Yun, Kim, Gi-Young, Chang, Young-Chae, Moon, Sung-Kwon, Kim, Wun-Jae, Choi, Yung Hyun
Format: Article
Language:English
Subjects:
Acetylcysteine
Activation
Anticancer properties
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Apoptosis - genetics
Argemone mexicana
BAX protein
bcl-2-Associated X Protein - genetics
bcl-2-Associated X Protein - metabolism
Benzophenanthridines - pharmacology
BH3 Interacting Domain Death Agonist Protein - genetics
BH3 Interacting Domain Death Agonist Protein - metabolism
Biochemistry
Biology
Bladder
Bladder cancer
c-Jun protein
Cancer
Cancer cells
Cancer prevention
Cancer therapies
Cancer treatment
Caspases - genetics
Caspases - metabolism
Cell growth
Cell Line, Tumor
Cell Survival - drug effects
Cell Survival - genetics
Chelidonium majus
Chemistry
Cysteine
Deregulation
Down-Regulation - drug effects
Early Growth Response Protein 1 - genetics
Early Growth Response Protein 1 - metabolism
EGR-1 protein
Free radicals
Gene expression
Genes
Growth
Humans
Inhibition
Interception
Isoquinolines - pharmacology
JNK Mitogen-Activated Protein Kinases - genetics
JNK Mitogen-Activated Protein Kinases - metabolism
JNK protein
Kinases
Macleaya cordata
Medicine
Metabolism
Mitochondria
Oxidative stress
Oxygen
Physiology
Pretreatment
Proteins
Reactive oxygen species
Reactive Oxygen Species - metabolism
Ribonucleic acid
RNA
Sanguinaria canadensis
Sanguinarine
siRNA
Studies
Transcription factors
Tumor cell lines
Tumors
Up-regulation
Up-Regulation - drug effects
Up-Regulation - genetics
Urinary bladder
Urinary Bladder Neoplasms - drug therapy
Urinary Bladder Neoplasms - genetics
Urinary Bladder Neoplasms - metabolism
X-Linked Inhibitor of Apoptosis Protein - genetics
X-Linked Inhibitor of Apoptosis Protein - metabolism
XIAP protein
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:Although the effects of sanguinarine, a benzophenanthridine alkaloid, on the inhibition of some kinds of cancer cell growth have been established, the underlying mechanisms are not completely understood. This study investigated possible mechanisms by which sanguinarine exerts its anticancer action in cultured human bladder cancer cell lines (T24, EJ, and 5637). Sanguinarine treatment resulted in concentration-response growth inhibition of the bladder cancer cells by inducing apoptosis. Sanguinarine-induced apoptosis was correlated with the up-regulation of Bax, the down-regulation of Bid and XIAP, the activation of caspases (-3, -8, and -9), and the generation of increased reactive oxygen species (ROS). The ROS scavenger N-acetyl cysteine (NAC) completely reversed the sanguinarine-triggered apoptotic events. In addition, sanguinarine effectively increased the activation of the c-Jun N-terminal kinase (JNK) and the expression of the early growth response gene-1 (Egr-1), which was recovered by pretreatment with NAC. Furthermore, knockdown of Egr-1 expression by small interfering RNA attenuated sanguinarine-induced apoptosis, but not the JNK inhibitor, indicating that the interception of ROS generation blocked the sanguinarine-induced apoptotic effects via deregulation of the expression of Egr-1 proteins. Taken together, the data provide evidence that sanguinarine is a potent anticancer agent, which inhibits the growth of bladder cancer cells and induces their apoptosis through the generation of free radicals.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0063425