Theanine and glutamate transporter inhibitors enhance the antitumor efficacy of chemotherapeutic agents

Sugiyama, Tomomi; Sadzuka, Yasuyuki

doi:10.1016/s0304-419x(03)00031-3

Cited by 49 publications

(48 citation statements)

References 44 publications

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“…(Moghaddam et al 1990;Yadid et al 1993;Koga and Momiyama 2000). Because the chemical structure of theanine is similar to glutamic acid, some studies of theanine examined its relationship to glutamic acid function and metabolism (Sugiyama et al 2003;Kakuda et al 2002a;Tsuge et al 2003;Oda et al 1980); however, the glutamate receptor antagonist MK-801 did not affect the increase of dopamine concentration by theanine injection in the rat striatum (Yokogoshi et al 1998a). This result suggested that theanine did not affect glutamate neurotransmission.…”

Section: Discussionmentioning

confidence: 99%

“…1). Therefore, the purpose of many recent studies on theanine was to determine whether the effects of theanine are related to its metabolism to glutamic acid (Sugiyama and Sadzuka 2003;Kakuda et al 2002a;Tsuge et al 2003). Using an in vivo brain microdialysis method, we showed that direct administration of theanine into the rat brain striatum enhanced the release of dopamine (Yokogoshi et al 1998a).…”

Section: Introductionmentioning

confidence: 99%

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Theanine, γ-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats

et al. 2008

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Theanine (c-glutamylethylamide) is one of the major amino acid components in green tea and can pass through the blood-brain barrier. Recent studies suggest that theanine affects the mammalian central nervous system; however, the detailed mechanism remains unclear. In this study, we demonstrated the effect of theanine on neurotransmission in the brain striatum by in vivo brain microdialysis. Theanine injection into the rat brain striatum did not increase the concentration of excitatory neurotransmitters in the perfusate. On the other hand, theanine injection increased the concentration of glycine in the perfusate. Because it has been reported that theanine promotes dopamine release in the rat striatum, we investigated the glycine and dopamine concentrations in the perfusate. Co-injection of glycine receptor antagonist, strychnine, reduced theanine-induced changes in dopamine. Moreover, AMPA receptor antagonist, which regulates glycine and GABA release from glia cells, inhibited these effects of theanine and this result was in agreement with the known inhibitory effect of theanine at AMPA receptors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Theanine, γ-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats

et al. 2008

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confidence: 99%

“…6) This action is due to the glutamate transporter expressed in the tumor cell membrane and is dependent on the influx inhibition of glutamate by theanine inhibition of this transporter and the resulting decrease in glutathione (GSH) synthesis. 7) Theanine did not increase DOX-induced adverse reactions in normal tissue, whereas reduced its adverse effects, and was therefore effective in enhancing the antitumor effect while decreasing the adverse effects of antitumor drugs.…”

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confidence: 99%

The Effect of Taurine, a Novel Biochemical Modulator, on the Antitumor Activity of Doxorubicin

Sadzuka

Matsuura

Sonobe

2009

Biological & Pharmaceutical Bulletin

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In cancer therapy, novel chemotherapeutic agents are being developed continually, 1) however, cancer-induced lethality is still high in many countries because of recalcitrant tumors and the appearance of resistant tumors. Furthermore, adverse reactions by antitumor drugs not only inhibit the therapeutic index but also require the use of combined agents to decrease these adverse reactions and the quality of life (QOL) of patients can worsen. While the development of novel antitumor drugs is a long and costly process, increasing the effectiveness of current therapies is also very important and should be addressed in clinical trials. As an example combined medicines, such as p-glycoprotein inhibitor in resistant tumors, have been used to increase the effectiveness of current antitumor agents. [2][3][4] From the viewpoint of biochemical modulation, combined medicines such as Tegaful have been applied in clinical therapy. However, it has been reported that some combined therapies increase the adverse effects of antitumor drugs as the antitumor effect increases, 5) and effective enhancement of the therapeutic index is not achieved. Furthermore, the QOL of patients can be affected negatively by many medicines. It is hoped to increase antitumor agent activity by combining antitumor therapies with foods that do not show adverse reactions or decrease QOL.From such a viewpoint, it was reported previously that theanine, an amino acid peculiar to green tea, has properties to increase the efficacy of doxorubicin (DOX) as an antitumor drug. 6) This action is due to the glutamate transporter expressed in the tumor cell membrane and is dependent on the influx inhibition of glutamate by theanine inhibition of this transporter and the resulting decrease in glutathione (GSH) synthesis. 7)Theanine did not increase DOX-induced adverse reactions in normal tissue, whereas reduced its adverse effects, and was therefore effective in enhancing the antitumor effect while decreasing the adverse effects of antitumor drugs. It is expected that there are other compounds with similar effectiveness, such as an amino acids or peptides, in other foods.Taurine (2-amino ethanesulfonic acid) is a major amino acid in fish and is found in all mammalian tissues. In clinical therapy, taurine is used to protect the liver and improve function with congestive cardiac failure. This study investigated the effect of taurine on the tumor cell permeability of DOX in vitro, studied its action on the antitumor effect of DOX in vivo, and elucidated the novel effect of taurine to increase DOX-induced antitumor activity. MATERIALS AND METHODSChemicals Taurine, b-alanine was purchased from Wako Pure Chemical Industries, Ltd. (Tokyo, Japan). DOX 10 mg/vial (Adriacin), was purchased from Kyowa Fermentation, Inc. (Tokyo, Japan). RPMI 1640 medium was purchased from Nissui Pharmaceutical Co., Ltd. (Tokyo, Japan). [ 3 H]-Taurine (9.5 MBq/mmol) was purchased from Amersham (Tokyo, Japan). Scintillation cocktail Scientisol Ex-H ® , balanine, and g-amino butyric acid (GABA) wer...

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“…8) A cooperative effect of theanine with several antitumor agents has also been reported. [9][10][11][12] These findings suggest that demand for theanine will become great as a supplement for improving and/or maintaining human health. Although several methods for preparing theanine have been reported, [13][14][15][16][17] they are usually complicated and show unsatisfactory yield.…”

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confidence: 99%

Cloning and Expression ofPseudomonas taetrolensY-30 Gene Encoding Glutamine Synthetase: An Enzyme Available for Theanine Production by Coupled Fermentation with Energy Transfer

Yamamoto

Wakayama

Tachiki

2006

Bioscience, Biotechnology, and Biochemistry

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Theanine and glutamate transporter inhibitors enhance the antitumor efficacy of chemotherapeutic agents

Cited by 49 publications

References 44 publications

Theanine, γ-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats

Theanine, γ-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats

The Effect of Taurine, a Novel Biochemical Modulator, on the Antitumor Activity of Doxorubicin

Cloning and Expression ofPseudomonas taetrolensY-30 Gene Encoding Glutamine Synthetase: An Enzyme Available for Theanine Production by Coupled Fermentation with Energy Transfer

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