Inhibitory effect of pisosterol on human glioblastoma cell lines with C-MYC amplification.

Abstract

Despite the remarkable progress in the characterization of the molecular pathogenesis of glioblastoma multiforme (GBM), these tumors remain incurable and, in most cases, refractory to aggressive cytotoxic treatments. We conducted a morphological and cytogenetic study in two GBM cell lines (U343 and AHOL1), before and after treatment with pisosterol (at 0.5, 1.0 and 1.8 µg ml⁻¹), a triterpene isolated from the fungus Pisolithus tinctorius. No significant alteration was observed in the morphology and frequency of chromosomal abnormalities in the cell lines analyzed after treatment with pisosterol. Using fluorescence in situ hybridization analysis with a locus-specific probe for C-MYC showed that 72% of U343 and 65% of AHOL1 cells contained more than two alleles of C-MYC before treatment. After treatment, no effects were detected at lower concentrations of pisosterol (0.5 and 1.0 µg ml⁻¹). However, at 1.8 µg ml⁻¹ of pisosterol, only 33% of U343 cells and 15% of AHOL1 cells presented more than two fluorescent signals, suggesting that pisosterol blocks the cells with gene amplification. Cells that do not show a high degree of C-MYC gene amplification 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: Edmundo L R Pereira, Patrícia D L Lima, André S Khayat, Marcelo O Bahia, Franciglauber S Bezerra, Manoel Andrade-Neto, Raquel C Montenegro, Cláudia Pessoa, Letícia V Costa-Lotufo, Manoel O Moraes, France K N Yoshioka, Giovanny R Pinto, Rommel R Burbano
• Journal: Journal of applied toxicology : JAT (J Appl Toxicol) Vol. 31 Issue 6 Pg. 554-60 (Aug 2011) ISSN: 1099-1263 [Electronic] England
• PMID: 21061448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 John Wiley & Sons, Ltd.

Chemical References

• Antineoplastic Agents
• Terpenes
• pisosterol

Topics

• Alleles
• Antineoplastic Agents (pharmacology)
• Basidiomycota (chemistry)
• Cell Line, Tumor
• Chromosome Aberrations (drug effects)
• Gene Amplification
• Genes, myc
• Glioblastoma (pathology)
• Humans
• In Situ Hybridization, Fluorescence
• Terpenes (pharmacology)