Anserine induced advantage effects on the antitumor activity of doxorubicin.
It is hoped that the strategy for the increase of antitumor activity by the combination of foods or their components will take quality of life into consideration. We examined whether anserine, is a dipeptide in foods, has beneficial effects on the doxorubicin (DOX) induced antitumor activity in vitro and in vivo. Anserine increased the DOX induced antitumor activity by the maintained DOX concentration in the tumor in vivo. On the other hand, anserine has no effect on the DOX concentration in normal tissues. Namely, it is expected that anserine will not increase the DOX induced adverse reaction. Thus, anserine appeared to increase the antitumor activity of DOX with an increased DOX concentration in the tumor by specific action on the tumor. Furthermore, anserine significantly induced DOX influx compared to that of the DOX alone group in vitro. It is speculated that the anserine induced increase in the antitumor activity of DOX in vivo was affected by the promotion of DOX influx into the tumor cells in vitro. Anserine was considered to take into tumor cells via a dipeptide transporter, and it resulted in an increase of the DOX influx. Anserine did not affect on the activity of the CYP3A subtype as a DOX metabolizing enzyme. Namely, it was expected that anserine increased the antitumor activity of DOX by the change of the DOX concentration without the changing metabolism of DOX.
Sadzuka
Yasuyuki
Y
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada Suruga-ku, Shizuoka 422-8526, Japan. sadzuka@u-shizuoka-ken.ac.jp
Sonobe
Takashi
T
D000818:Animals; D000861:Anserine / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism
D000970:Antineoplastic Agents; D007527:Isoenzymes; D004317:Doxorubicin; D003577:Cytochrome P-450 Enzyme System; D000861:Anserine