Anticancer Effects of Synthetic Phosphoethanolamine on Ehrlich Ascites Tumor: An Experimental Study

Autor(es)

Ferreira, Adilson Kleber ^{[1, 2]} ; Meneguelo, Renato ^[3] ; Pereira, Alexandre ^[4] ; Filho, Otaviand Mendonca R. ^[5] ; Chierice, Gilberto Orivaldo ^[3] ; Maria, Durvanei Augusto ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Butantan Inst, Biochem & Biophys Lab, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, BR-05508 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept Chem & Polymers Technol, Sao Carlos, SP - Brazil

^[4] Butantan Inst, Genet Lab, Sao Paulo - Brazil

^[5] Univ Uberaba, Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ANTICANCER RESEARCH; v. 32, n. 1, p. 95-104, JAN 2012.
• Citações Web of Science: 26

Resumo

Background: Antineoplastic phospholipids (ALPs) represent a promising class of drugs with a novel mode of action undergoes rapid turnover in the cell membrane of tumors, interfering with lipid signal transduction, inducing cell death. The aim of this study was to investigate the synthetic phosphoethanolamine (Pho-s) as a new anticancer agent. Materials and Methods: Cell viability and morphology were assessed by (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Hoechst and rhodamine staining. Apoptosis was assessed by Annexin V and propidium iodide (PI) staining, caspase-3 activity, mitochondrial membrane potential (Delta m psi) and cell cycle analysis, combined with evaluation of tumor growth in Ehrlich Ascites Tumor (EAT) bearing mice. Results: We found that Pho-s 2.30 mg/ml induced cytotoxicity in all tumor cell lines studied without affecting normal cells. In vitro studies with EAT cells indicated that Pho-s induced apoptosis, demonstrated by an increase in Annexin-V positive cells, loss of mitochondrial potential (Delta m psi) and increased caspase-3 activity. It was also shown to increase the sub-G(1) apoptotic fraction and inhibit progression to the S phase of the cell cycle. Additionally, antitumor effects on the EAT-bearing mice showed that Pho-s, at a concentration of 35 and 70 mg/kg, inhibited tumor growth and increased the lifespan of animals without causing liver toxicity. Conclusion: These findings suggest that Pho-s is a potential anticancer candidate drug. (AU)

• Processo FAPESP: 10/50220-9 - Alquil fosfatado sintético precursor dos fosfolipídios de membrana celular com potencial efeito antitumoral e apoptótico em modelos de tumores experimentais
• Beneficiário: Adilson Kleber Ferreira
• Linha de fomento: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 07/50571-3 - Avaliacao das propriedades anti-tumorais da fosfoetanolamina sintetica in vitro e in vivo no melanoma b16f10.
• Beneficiário: Adilson Kleber Ferreira
• Linha de fomento: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 08/56089-1 - Avaliacao das propriedades antitumorais e apoptoticas da fosfoetanolamina sintetica em modelos experimentais
• Beneficiário: Adilson Kleber Ferreira
• Linha de fomento: Bolsas no Brasil - Mestrado