title: [Glutamate transporter mediated increase of antitumor activity by theanine, an amino acid in green tea].
abstract: We have confirmed that theanine, a major amino acid in green tea, enhances the antitumor activity of doxorubicin (DOX) without an increase in DOX-induced side effects. We believe that the action of theanine is due to decreases in glutamate uptake via inhibition of the glutamate transporter, intracellular glutathione (GSH) synthesis, GS-DOX conjugate level, and subsequent extracellular transport of GS-DOX by the MRP5/GS-X pump. To increase the clinical usefulness of theanine, we examined its effects on the antitumor activity of cisplatin and irinotecan (CPT-11), which a known to be transported by the efflux system related to MRP. Cisplatin decreased tumor volume in M5076 tumor-bearing mice. Furthermore, the combination of theanine with cisplatin increased the decrease in tumor volume as compared with the cisplatin-alone group. Tumor volume in the CPT-11-alone group did not show a decrease, but the combination of theanine with CPT-11 significantly reduced tumor volume. The concentration of cisplatin in the tumor was significantly increased by combination with theanine, and thus we assume that it correlated with the enhancement on the antitumor activity of theanine. On the other hand, changes in drug concentrations with theanine were not observed in normal tissues, but rather it is indicated that theanine tends to reduce their concentrations. Therefore theanine enhances the antitumor activity not only of DOX but also of cisplatin or CPT-11.
authors.affiliation: University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan. sadzuka@u-shizuoka-ken.ac.jp
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sadzuka
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kishimoto
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Sonobe
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002945:Cisplatin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003864:Depression, Chemical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005971:Glutamates / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000096:biosynthesis; D000077146:Irinotecan; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000378:metabolism; D013662:Tea; D014018:Tissue Distribution
chemical_list: D027322:Amino Acid Transport System X-AG; D000970:Antineoplastic Agents; D005971:Glutamates; D013662:Tea; D000077146:Irinotecan; C026166:theanine; D005978:Glutathione; D002945:Cisplatin; D002166:Camptothecin