Document Detail


Involvement of caspase and MAPK activities in norcantharidin-induced colorectal cancer cell apoptosis.
MedLine Citation:
PMID:  20040369     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Norcantharidin exhibits cytotoxicity in many cancer cell lines, including colorectal cancer (CRC) cells. Its cytotoxic potency on primary CRC cells and other normal constituent cells of the human body remains elusive. This study investigates whether norcantharidin differentially exhibits cytotoxicity on primarily isolated CRC cells and dermal fibroblasts. The in vitro chemosensitivity of norcantharidin was measured using a MTT tetrazolium assay and compared with 73 primary tumor cells from surgically excised colorectal tumors, six human CRC cell lines and dermal fibroblasts. Observations of cytotoxicity to primary tumor cells reveal significant differences among genders and histological types; however, drug-induced chemosensitivity was not correlated with age or clinical stages of CRC patients. Norcantharidin had a similar cytotoxic effect on primary tumor cells and CRC cell lines in a dose-dependent manner. In contrast, normal fibroblasts were more resistant to norcantharidin-induced cytotoxicity than CRC cells. DAPI staining results demonstrated that norcantharidin caused CRC cell apoptosis by nuclear fragmentation and chromatin condensation. The release of cytochrome c and the triggering of caspase-3, -8 and -9 activation mediated apoptotic induction. Conversely, pretreatment with caspases or mitogen-activated protein kinase (MAPK) inhibitors significantly suppressed norcantharidin-induced CRC cytotoxicity. These in vitro results suggest that norcantharidin may be a safe and effective anti-cancer drug for CRC.
Authors:
Pei-Yu Yang; Ming-Feng Chen; Chi-Hong Tsai; Dan-Ning Hu; Fang-Rong Chang; Yang-Chang Wu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-28
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  24     ISSN:  1879-3177     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-09     Completed Date:  2010-06-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  766-75     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2009 Elsevier Ltd. All rights reserved.
Affiliation:
Graduate Institute of Natural Products, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan, ROC. peyyuh@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Aged
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Bicyclo Compounds, Heterocyclic / pharmacology*
Blotting, Western
Caspases / metabolism,  physiology*
Cell Line, Tumor
Colorectal Neoplasms / drug therapy*,  pathology
Cytochromes c / metabolism
DNA Fragmentation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Enzyme-Linked Immunosorbent Assay
Female
Fibroblasts / drug effects
Fluorescent Dyes
Histones / metabolism
Humans
Indoles
Male
Middle Aged
Mitogen-Activated Protein Kinases / metabolism,  physiology*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Bicyclo Compounds, Heterocyclic; 0/Fluorescent Dyes; 0/Histones; 0/Indoles; 47165-04-8/DAPI; 5442-12-6/norcantharidin; 9007-43-6/Cytochromes c; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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