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J.Health Sci., 54(6), 654-660, 2008
Isolation of Ursolic Acid from Apple Peels and Its Specific Efficacy as a Potent Antitumor Agent
Hideaki Yamaguchi,*, a Toshiro Noshita,b
Yumi Kidachi,b Hironori Umetsu,c
Masahiko Hayashi,d Kanki Komiyama,d
Shinji Funayama,e and Kazuo Ryoyamab
aDepartment of Pharmacy, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku, Nagoya 468-8503, Japan,
bDepartment of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Aomori University, 2-3-1 Kobata, Aomori 030-0943, Japan,
cLaboratory of Food Chemistry, Department of Life Sciences, Junior College, Gifu Shotoku Gakuen University, 1-38 Nakauzura, Gifu 500-8288, Japan,
dThe Kitasato Institute, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan, and
eDepartment of Kampo Pharmaceutical Sciences, Nihon Pharmaceutical University, 10281 Inamachi-Komuro, Saitama 362-0806, Japan
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/m HM-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.
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