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Basic apoptotic and necrotic cell death in human liver carcinoma (HepG(2) ) cells induced by synthetic azamacrocycle.
MedLine Citation:
PMID:  22644747     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Treatment of diseases with synthetic materials has been an aspiration of mankind since the dawn of human development. In this research, three complex compounds of azamacrocycle (TD1, TD2, and TD3) were synthesized, and experiments were conducted to determine whether their toxicity to human liver carcinoma (HepG(2) ) cells is associated with apoptotic and/or necrotic cell death. Cell survival was determined by MTT assay. Apoptosis and necrosis were measured by annexin V FITC/PI assay using the flow cytometry and by propidium iodide (PI) assay using the cellometer vision. HepG(2) cells were treated with different concentrations of azamacrocycles for 48 h. Results from MTT assay indicated that all the three azamacrocycles significantly (p < 0.05) reduce cell viability in a dose-dependent manner, showing 48 h-LD(50) values of about 37.97, 33.60, and 19.29 μM, for TD3, TD1 and TD2, respectively. Among the three compounds tested, TD2 showed the most pronounced cytotoxic activity against HepG(2) cells, being about twofold more potent than TD3. The order of toxicity was TD2 > TD1 > TD3. Because TD2 exerted the most cytotoxic activity against HepG(2) cells, it was used in the subsequent apoptosis and necrosis-related experiments. The flow cytometry assessment showed a strong dose-response relationship with regard to TD2 exposure and annexin V/PI positive cells. PI assay data indicated that TD2 exposure increased the proportion of fluorescence positive cells. Overall, our results indicate that azamacrocycle toxicity to HepG(2) cells is associated with apoptotic and necrotic cell death resulting from phosphatidylserine externalization and loss of membrane integrity. © 2012 Wiley Periodicals, Inc. Environ Toxicol, 2012.
Authors:
Clement G Yedjou; Musabbir A Saeed; Md Alamgir Hossain; Waneene Dorsey; Hongtao Yu; Paul B Tchounwou
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-30
Journal Detail:
Title:  Environmental toxicology     Volume:  -     ISSN:  1522-7278     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100885357     Medline TA:  Environ Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Affiliation:
Cellomics and Toxicogenomics Research Laboratory, NIH-RCMI Center for Environmental Health, Jackson State University, 1400 Lynch Street, P.O. Box 18540, Jackson, Mississippi 39217, USA.
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