Anticancer effects of synthetic phosphoethanolamine on Ehrlich ascites tumor: an experimental study.
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.


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 (ΔmΨ) 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 (ΔmΨ) 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.


CONCLUSIONS
These findings suggest that Pho-s is a potential anticancer candidate drug.
Biochemistry and Biophysical Laboratory, Butantan Institute, Sao Paulo, Brazil.
Adilson Kleber
AK
Ferreira
Renato
R
Meneguelo
Alexandre
A
Pereira
Otaviano  R
O
Mendonça Filho
Gilberto Orivaldo
GO
Chierice
Durvanei Augusto
DA
Maria
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004983:Ethanolamines / Q000627:therapeutic use*; D005434:Flow Cytometry; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D015996:Survival Rate
D004983:Ethanolamines; C005448:phosphorylethanolamine; D053148:Caspase 3