Pisosterol induces interphase arrest in HL60 cells with c-MYC amplification. 2010

T C R Silva, and P D L Lima, and M O Bahia, and A S Khayat, and F S Bezerra, and M Andrade-Neto, and A D Seabra, and T B Pontes, and M O Moraes, and R C Montenegro, and L V Costa-Lotufo, and C Pessoa, and G R Pinto, and R R Burbano
Human Cytogenetics Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém/PA, Brazil.

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.

UI MeSH Term Description Entries
D007399 Interphase The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs). Interphases
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005784 Gene Amplification A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication. Amplification, Gene
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000090063 Proto-Oncogene Mas A protein that is encoded by the MAS1 gene. It is a receptor for ANGIOTENSIN 1-7 and acts as an antagonist of ANGIOTENSIN-2 TYPE 1 RECEPTOR. C-Mas Protein,II-Proto-Oncogene Proteins, Cellular,Mas Protein,Mas1 Protein,Proto-Oncogene Protein Mas,Proto-Oncogene Proteins C-Mas-1,C Mas Protein,C-Mas-1, Proto-Oncogene Proteins,Cellular II-Proto-Oncogene Proteins,II Proto Oncogene Proteins, Cellular,Mas, Proto-Oncogene,Protein Mas, Proto-Oncogene,Protein, C-Mas,Protein, Mas,Protein, Mas1,Proteins, Cellular II-Proto-Oncogene,Proto Oncogene Mas,Proto Oncogene Proteins C Mas 1
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D013729 Terpenes A class of compounds composed of repeating 5-carbon units of HEMITERPENES. Isoprenoid,Terpene,Terpenoid,Isoprenoids,Terpenoids
D015972 Gene Expression Regulation, Neoplastic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue. Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic
D016271 Proto-Oncogene Proteins c-myc Basic helix-loop-helix transcription factors encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis. L-myc Proteins,N-myc Proteins,c-myc Proteins,myc Proto-Oncogene Proteins,p62(c-myc),Proto-Oncogene Products c-myc,Proto-Oncogene Proteins myc,myc Proto-Oncogene Product p62,p62 c-myc,L myc Proteins,N myc Proteins,Proteins myc, Proto-Oncogene,Proto Oncogene Products c myc,Proto Oncogene Proteins c myc,Proto Oncogene Proteins myc,Proto-Oncogene Proteins, myc,c myc Proteins,myc Proto Oncogene Product p62,myc Proto Oncogene Proteins,myc, Proto-Oncogene Proteins,p62 c myc

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