title: Antitumor potential of the myotoxin BthTX-I from Bothrops jararacussu snake venom: evaluation of cell cycle alterations and death mechanisms induced in tumor cell lines.
abstract: BACKGROUND
  Phospholipases A2 (PLA2s) are abundant components of snake venoms that have been extensively studied due to their pharmacological and pathophysiological effects on living organisms. This study aimed to assess the antitumor potential of BthTX-I, a basic myotoxic PLA2 isolated from Bothrops jararacussu venom, by evaluating in vitro processes of cytotoxicity, modulation of the cell cycle and induction of apoptosis in human (HL-60 and HepG2) and murine (PC-12 and B16F10) tumor cell lines.
  
  
  METHODS
  The cytotoxic effects of BthTX-I were evaluated on the tumor cell lines HL-60 (promyelocytic leukemia), HepG2 (human hepatocellular carcinoma), PC-12 (murine pheochromocytoma) and B16F10 (murine melanoma) using the MTT method. Flow cytometry technique was used for the analysis of cell cycle alterations and death mechanisms (apoptosis and/or necrosis) induced in tumor cells after treatment with BthTX-I.
  
  
  RESULTS
  It was observed that BthTX-I was cytotoxic to all evaluated tumor cell lines, reducing their viability in 40 to 50 %. The myotoxin showed modulating effects on the cell cycle of PC-12 and B16F10 cells, promoting delay in the G0/G1 phase. Additionally, flow cytometry analysis indicated cell death mainly by apoptosis. B16F10 was more susceptible to the effects of BthTX-I, with ~40 % of the cells analyzed in apoptosis, followed by HepG2 (~35 %), PC-12 (~25 %) and HL-60 (~4 %).
  
  
  CONCLUSIONS
  These results suggest that BthTX-I presents antitumor properties that may be useful for developing new therapeutic strategies against cancer.
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Avenida do Café, s/n, Ribeirão Preto, SP CEP 14040-903 Brazil.
authors.forename: Cássio
authors.initials: C
authors.lastname: Prinholato da Silva
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Avenida do Café, s/n, Ribeirão Preto, SP CEP 14040-903 Brazil.
authors.forename: Tássia R
authors.initials: TR
authors.lastname: Costa
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Avenida do Café, s/n, Ribeirão Preto, SP CEP 14040-903 Brazil.
authors.forename: Raquel M Alves
authors.initials: RM
authors.lastname: Paiva
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Avenida do Café, s/n, Ribeirão Preto, SP CEP 14040-903 Brazil.
authors.forename: Adélia C O
authors.initials: AC
authors.lastname: Cintra
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Avenida do Café, s/n, Ribeirão Preto, SP CEP 14040-903 Brazil.
authors.forename: Danilo L
authors.initials: DL
authors.lastname: Menaldo
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Avenida do Café, s/n, Ribeirão Preto, SP CEP 14040-903 Brazil.
authors.forename: Lusânia M Greggi
authors.initials: LM
authors.lastname: Antunes
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Avenida do Café, s/n, Ribeirão Preto, SP CEP 14040-903 Brazil.
authors.forename: Suely V
authors.initials: SV
authors.lastname: Sampaio
keywords: Antitumor potential; Apoptosis; Bothrops jararacussu; BthTX-I; Cell cycle alterations