Inhibitory effect of pisosterol on human glioblastoma cell lines with C-MYC amplification.
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.
Human Cytogenetics Laboratory, Institute of Biological Sciences, Federal University of Pará, Av. Augusto Corrêa, 01, CEP 66075-110 - Belém/PA, Brazil.
Edmundo L R
EL
Pereira
Patrícia D L
PD
Lima
André S
AS
Khayat
Marcelo O
MO
Bahia
Franciglauber S
FS
Bezerra
Manoel
M
Andrade-Neto
Raquel C
RC
Montenegro
Cláudia
C
Pessoa
Letícia V
LV
Costa-Lotufo
Manoel O
MO
Moraes
France K N
FK
Yoshioka
Giovanny R
GR
Pinto
Rommel R
RR
Burbano
D000483:Alleles; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001487:Basidiomycota / Q000737:chemistry; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations / Q000187:drug effects; D005784:Gene Amplification; D016259:Genes, myc; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D013729:Terpenes / Q000494:pharmacology*
D000970:Antineoplastic Agents; D013729:Terpenes; C522992:pisosterol