title: Differential genotoxicity and cytotoxicity of phomoxanthone A isolated from the fungus Phomopsis longicolla in HL60 cells and peripheral blood lymphocytes.
abstract: Phomoxanthone A (PhoA) is a compound isolated from the endophytic fungus Phomopsis longicolla, associated with marine algae Bostrychia radicans. Although this metabolite was previously described regarding its high biological potential, there are no reports concerning the effects of this compound on DNA integrity. This study aimed to evaluate, in lymphocytes and promyelocytic leukemia HL60 cells, the cytotoxicity of this compound through MTT and neutral red (NR) assays, as well as its genotoxicity and mutagenicity by alkaline comet assay and cytokinesis-block micronucleus cytome assay (CBMN-Cyt), respectively. Cells were treated with PhoA concentrations ranging from 0.01 to 100.0μg/mL, and the results show that this molecule did not exhibit cytotoxicity, genotoxicity or mutagenicity in lymphocytes at any tested concentration. Furthermore, PhoA was highly cytotoxic, genotoxic and mutagenic to HL60 cells, establishing a differential response of this natural product in normal and cancer cells. PhoA was highly selective towards HL60 compared to lymphocytes, causing no damage in the latter cell line, suggesting that this compound could be a promising compound in antitumoral drug development.
authors.affiliation: Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Gabriel Brolio
authors.initials: GB
authors.lastname: Pavão
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Vinícius Paula
authors.initials: VP
authors.lastname: Venâncio
authors.affiliation: Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Ana Ligia Leandrini
authors.initials: AL
authors.lastname: de Oliveira
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Lívia Cristina
authors.initials: LC
authors.lastname: Hernandes
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Mara Ribeiro
authors.initials: MR
authors.lastname: Almeida
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Lusânia Maria Greggi
authors.initials: LM
authors.lastname: Antunes
authors.affiliation: Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: hosana@fcfrp.usp.br.
authors.forename: Hosana Maria
authors.initials: HM
authors.lastname: Debonsi
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000633:toxicity*; D001203:Ascomycota / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020552:Comet Assay; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D015162:Micronucleus Tests; D009153:Mutagens / Q000302:isolation & purification / Q000633:toxicity*; D044004:Xanthones / Q000302:isolation & purification / Q000633:toxicity*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D009153:Mutagens; D044004:Xanthones; C436332:phomoxanthone A
keywords: Comet assay; Endophytic fungi; Genotoxicity; MTT; Marine natural products