Isolation of ursolic acid from apple peels and its specific efficacy as a potent antitumor agent

Abstract

Dried apple peels were extracted with n-hexane, chloroform, and methanol successively. The portion of the chloroform extract that showed the strongest cytotoxic activity was purified by silica gel chromatography to isolate ursolic acid (UA). The amount of the isolated UA was 0.71% of the dried peels. Normal mouse embryo cells [serum-free mouse embryo (SFME) cells] and tumorigenic human c-Ha-ras-and mouse c-myc-transformed SFME cells [r/m highly metastatic (HM)-SFME-1 cells] were treated with various concentrations of UA (2.5-20 μM) to investigate its effects on cell growth. UA at 10 μM appeared very effective at suppressing the tumor cell growth, affecting more than 82% of r/mHM-SFME-1 cells, while it inhibited cell growth in only about 7% of SFME cells. Tumorigenic r/m HM-SFME-1 cells were also treated with various concentrations (2.5-10 μM) of epidermal growth factor (EGF) or aminoguanidine (AG) in the presence of UA (2.5-10 μM). Neither EGF nor AG seemed to have any effect on UA-inhibited cell growth. In the present study, it is revealed that UA could be a very effective and promising agent for antitumor treatments, as it specifically affects tumorigenic cells yet appears to cause very little harm to normal cells.