Article

Shikonin analogue (SA) 93/637 induces apoptosis by activation of caspase-3 in U937 cells.

Center for Combat Casualty and Life Sustainment Research, Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Frontiers in Bioscience (impact factor: 3.52). 02/2008; 13:561-8. pp.561-8
Source: PubMed

ABSTRACT Beta,beta-dimethyl acryl shikonin is an extract from the root of plant Arnebia nobilis which has been shown to possess anti-cancer activity. However, its toxicity limited further development of shikonin as a therapeutic agent. Subsequently, several analogues of beta,beta-dimethyl acryl shikonin were synthesized. One of these analogues, shikonin 93/637 was found to be significantly less toxic compared to shikonin. This study is aimed to determine the cell cycle associated differences in the susceptibility of U937 cells to apoptosis induced by shikonin analogue 93/637 (SA). Lower concentrations of SA (approximately 100 nM) showed no significant changes in cell growth. However, higher concentrations (approximately 500 nM) resulted in growth inhibition of U937 cells after 48 h of treatment with SA as measured by MTT assay. Flow cytometric analysis showed that SA treatment resulted in blocking of cell cycle progression in G1 phase. Decreased expression of Cyclin D, CDK 4 and PCNA was observed with SA treatment corroborating the G1 block. DNA gel electrophoresis showed an oligonucleotide ladder pattern, a distinct characteristic of DNA fragmentation associated with programmed cell death. Ribonuclease protection assay revealed inhibition of bcl2 expression at transcriptional level. SA treatment also resulted in induction of caspase-3 activity. The results suggest the involvement of bcl2 and Caspase-3 in SA induced apoptosis of human U937 cells.

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    Article: Noteworthy Secondary Metabolites Naphthoquinones-their Occurrence, Pharmacological Properties and Analysis
    Petr Babula, Vojtech Adam, Ladislav Havel, Rene Kizek
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    ABSTRACT: Chemical investigation of many bacterial and fungal, as well as plant species has revealed the presence of in-teresting compounds derived from naphthalene – 1,4-naphthoquinones and rarely also 1,2-naphthoquinones. They were detected in many species of families Bignoniaceae, Droseraceae, Plumbaginace, Boraginaceae, Juglandaceae as well as in species of small families, such as Dioncophyllaceae or Acanthaceae. Naphthoquinones have very interesting spectrum of biological actions, including antibiotic, antiviral, anti-inflammatory, antipyretic, antiproliferative and cytotoxic effects. Because of these properties the plants containing them are used in folk medicines, mainly by natives in Asia, where espe-cially Chinese medicine uses aerial as well as subterranean parts of these plants for hundreds years, and South America. The utilizing of naphthoquinones for medicinal purposes and their occurrence in nature is reviewed and discussed. Moreover, we review analytical techniques using for their analysis.
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Keywords

anti-cancer activity
 
bcl2 expression
 
caspase-3 activity
 
cell cycle progression
 
cell death
 
cell growth
 
Cyclin D
 
Decreased expression
 
DNA fragmentation
 
DNA gel electrophoresis
 
Flow cytometric analysis
 
G1 block
 
G1 phase
 
human U937 cells
 
MTT assay
 
oligonucleotide ladder pattern
 
plant Arnebia nobilis
 
Ribonuclease protection assay
 
SA induced apoptosis
 
SA treatment corroborating