The novel phenylester anticancer compounds: Study of a derivative of aspirin (phoshoaspirin).
We have synthesized a series of novel phenylester compounds and present our assessment of such a derivative of aspirin, 3-((diethoxyphosphoryloxy)methyl)phenyl 2-acetoxybenzoate, provisionally named phosphoaspirin. We determined its anticancer activity both in vitro and in vivo. Phosphoaspirin inhibited the growth of HT-29 human colon adenocarcinoma cells (IC(50) = 276.6+/-12.3 microM (mean +/- SEM)] through a combined antiproliferative and mainly proapoptotic effect. Phosphoaspirin (100 mg/kg body weight intraperitoneally daily for 21 days) also inhibited the growth of HT-29 tumors grown as xenografts in nude mice. The size of the tumors decreased progressively in the phosphoaspirin treated group, compared to controls, being reduced by 57% (p<0.001) on day 21. Phosphoaspirin achieved this effect by modulating cell kinetics; the proliferation index of cancer cells was reduced by 18.13% compared to controls (p<0.001) and the apoptosis index was increased by 94.6% (p<0.003). There was no apparent toxicity from phosphoaspirin. We conclude that phosphoaspirin is a promising agent for the control of cancer that deserves further evaluation.
Rigas
Basil
B
Division of Cancer Prevention, Stony Brook University, Stony Brook, NY 11794-5200, USA. basil.rigas@stonybrook.edu
Kozoni
Vasiliki
V
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D009569:Nitric Oxide / Q000502:physiology; D010755:Organophosphates / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D010755:Organophosphates; C527365:phosphoaspirin; D009569:Nitric Oxide; D001241:Aspirin