title: Pisosterol induces interphase arrest in HL60 cells with c-MYC amplification.
abstract: 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 microg/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 microg/mL). However, at 1.8 microg/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.
authors.affiliation: Human Cytogenetics Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém/PA, Brazil.
authors.forename: T C R
authors.initials: TC
authors.lastname: Silva
authors.forename: P D L
authors.initials: PD
authors.lastname: Lima
authors.forename: M O
authors.initials: MO
authors.lastname: Bahia
authors.forename: A S
authors.initials: AS
authors.lastname: Khayat
authors.forename: F S
authors.initials: FS
authors.lastname: Bezerra
authors.forename: M
authors.initials: M
authors.lastname: Andrade-Neto
authors.forename: A D
authors.initials: AD
authors.lastname: Seabra
authors.forename: T B
authors.initials: TB
authors.lastname: Pontes
authors.forename: M O
authors.initials: MO
authors.lastname: Moraes
authors.forename: R C
authors.initials: RC
authors.lastname: Montenegro
authors.forename: L V
authors.initials: LV
authors.lastname: Costa-Lotufo
authors.forename: C
authors.initials: C
authors.lastname: Pessoa
authors.forename: G R
authors.initials: GR
authors.lastname: Pinto
authors.forename: R R
authors.initials: RR
authors.lastname: Burbano
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C000715470:MAS1 protein, human; C489427:MYC protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D013729:Terpenes; C522992:pisosterol