Pisosterol induces interphase arrest in HL60 cells with C-MYC amplification

• Published in: Human & experimental toxicology 2010-03, Vol.29 (3), p.235-240
• Main Authors: Silva, TCR, Lima, PDL, Bahia, MO, Khayat, AS, Bezerra, FS, Andrade-Neto, M., Seabra, AD, Pontes, TB, Moraes, MO, Montenegro, RC, Costa-Lotufo, LV, Pessoa, C., Pinto, GR, Burbano, RR
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Antineoplastic Agents - pharmacology; Apoptosis; Biological and medical sciences; Cell culture; Cell cycle; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemotherapy; Dose-Response Relationship, Drug; Gene Amplification; Gene Expression Regulation, Neoplastic; HL-60 Cells; Humans; In Situ Hybridization, Fluorescence; Interphase; Leukemia; Medical sciences; Pharmacology. Drug treatments; Pisolithus tinctorius; Proto-Oncogene Proteins c-myc - genetics; Terpenes - pharmacology; Toxicology
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/0960327109359637

The leukaemia cell line HL60 is widely used in studies of the cell cycle, apoptosis and adhesion mechanisms in cancer cells. One marked characteristic of HL60 cells is the C-MYC proto-oncogene amplification, resulting in the formation of homogeneously staining regions (HSRs) at 8p24. We conducted a fluorescence in situ hybridization study in an HL60 cell line, using a locus-specific probe for C-MYC, before and after treatment with pisosterol (at 0.5, 1.0 and 1.8 μg/mL), a triterpene isolated from the fungus Pisolithus tinctorius. Before treatment, 87.5% of the cells showed HSRs. After treatment, no effects were detected at lower concentrations of pisosterol (0.5 and 1.0 μg/mL). However, at 1.8 μg/mL only 15% of the cells presented HSRs, and 39.5% presented few fluorescent signals (3 or 4 alleles), suggesting that pisosterol probably blocks the cells with HSRs at interphase. This result is particularly interesting because cells that do not show a high degree of C-MYC gene amplification have a less aggressive and invasive behaviour and are easy targets for chemotherapy. Therefore, further studies are needed to examine the use of pisosterol in combination with conventional anti-cancer therapy.