Document Detail


Cell cycle arrest induced by pisosterol in HL60 cells with gene amplification.
MedLine Citation:
PMID:  18465199     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The leukemia cell line HL60 is widely used in studies of the cell cycle, apoptosis, and adhesion mechanisms in cancer cells. We conducted a focused cytogenetic study in an HL60 cell line, by analyzing GTG-banded chromosomes before and after treatment with pisosterol (at 0.5, 1.0, and 1.8 microg/ml), a triterpene isolated from Pisolithus tinctorius, a fungus collected in the Northeast of Brazil. Before treatment, 99% of the cells showed the homogeneously staining region (HSR) 8q24 aberration. After treatment with 1.8 microg/ml pisosterol, 90% of the analyzed cells lacked this aberration. We further performed a pulse test, in which the cells treated with pisosterol (0.5, 1.0, and 1.8 microg/ml) were washed and re-incubated in the absence of pisosterol. Only 30% of the analyzed cells lacked the HSR 8q24 aberration, suggesting that pisosterol probably blocks the cells with HSRs at interphase. No effects were detected at lower concentrations. At the highest concentration examined (1.8 microg/ml), pisosterol also inhibited cell growth, but this effect was not observed in the pulse test, reinforcing our hypothesis that, at the concentrations tested, pisosterol probably does not induce cell death in the HL60 line. The results found for pisosterol were compared with those for doxorubicin. Cells that do not show a high degree of gene amplification (HSRs and double-minute chromosomes) have a less aggressive and invasive behavior and are easy targets for chemotherapy. Therefore, further studies are needed to examine the use of pisosterol in combination with conventional anti-cancer therapy.
Authors:
R R Burbano; P D L Lima; M O Bahia; A S Khayat; T C R Silva; F S Bezerra; M Andrade Neto; M O de Moraes; R C Montenegro; L V Costa-Lotufo; C Pessoa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-05-09
Journal Detail:
Title:  Cell biology and toxicology     Volume:  25     ISSN:  1573-6822     ISO Abbreviation:  Cell Biol. Toxicol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-05     Completed Date:  2009-06-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8506639     Medline TA:  Cell Biol Toxicol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  245-51     Citation Subset:  IM    
Affiliation:
Human Cytogenetics Laboratory, Institute of Biological Sciences, Federal University of Pará, Campus Universitário do Guamá, Pará, Brazil. rommel@ufpa.br
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / toxicity*
Basidiomycota / chemistry*
Cell Cycle / drug effects*
Chromosome Aberrations / drug effects
Chromosome Banding
Doxorubicin / toxicity
Drug Screening Assays, Antitumor
Gene Amplification / drug effects*
HL-60 Cells / drug effects*,  physiology
Humans
Leukemia, Promyelocytic, Acute / drug therapy*
Mitotic Index
Plant Extracts / toxicity
Terpenes / toxicity*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Plant Extracts; 0/Terpenes; 0/pisosterol; 23214-92-8/Doxorubicin

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


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