Glutamate transporter mediated increase of antitumor activity by theanine, an amino acid in green tea
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Recent studies report an anxiolytic effect of a single dose of theanine up to 200-250 mg per day, and it may be extended up to 1250 mg/day.
“Recent studies referred anxiolytic effect of single dose of theanine up to 200-250 mg per day and it may be extended up to 1 250 mg/day [9,12,[35][36][37] .”
From l -theanine: A potential multifaceted natural bioactive amide as health supplement (2017) · cites this paper as [9]
L-theanine enhances anti-tumor effects of cisplatin on mouse M5076 cells.
“Ltheanine enhances anti-tumor effects of cisplatin on mouse M5076 cells [9]”
From l -theanine: A potential multifaceted natural bioactive amide as health supplement (2017) · cites this paper as [9]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Yokogoshi, H., Kato, Y., Sagesaka, Y. M., Takihara-Matsuura, T., Kakuda, T., & Takeuchi, N. (1995) · Bioscience, Biotechnology, and Biochemistry · doi:10.1271/bbb.59.615 · Cited by 192 · see citing works
Effects of L-Theanine on the Release of .ALPHA.-Brain Waves in Human Volunteers.
KOBAYASHI, K., NAGATO, Y., AOI, N., JUNEJA, L. R., KIM, M., YAMAMOTO, T., & SUGIMOTO, S. (1998) · Journal of the agricultural chemical society of Japan · doi:10.1271/nogeikagaku1924.72.153 · Cited by 123 · see citing works
Metabolism of Theanine, γ-Glutamylethylamide, in Rats
Unno, T., Suzuki, Y., Kakuda, T., Hayakawa, T., & Tsuge, H. (1999) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf981113t · Cited by 109 · see citing works
Sadzuka, Y., Sugiyama, T., & Sonobe, T. (2000) · Toxicology Letters · doi:10.1016/s0378-4274(99)00290-8 · Cited by 99 · see citing works
Self-citationKIMURA, R., & MURATA, T. (1971) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.19.1257 · Cited by 98 · see citing works
Modulation of cancer chemotherapy by green tea.
Sadzuka, Y., Sugiyama, T., & Hirota, S. (1998) · PubMed · Cited by 80 · see citing works
Self-citationThe effects of theanine, as a novel biochemical modulator, on the antitumor activity of adriamycin
Sadzuka, Y., Sugiyama, T., Miyagishima, A., Nozawa, Y., & Hirota, S. (1996) · Cancer Letters · doi:10.1016/0304-3835(96)04282-6 · Cited by 68 · see citing works
Self-citationCombination of theanine with doxorubicin inhibits hepatic metastasis of M5076 ovarian sarcoma.
SUGIYAMA, T., & Sadzuka, Y. (1999) · PubMed · Cited by 67 · see citing works
Self-citationEnhancement of the activity of doxorubicin by inhibition of glutamate transporter
Sadzuka, Y., Sugiyama, T., Suzuki, T., & Sonobe, T. (2001) · Toxicology Letters · doi:10.1016/s0378-4274(01)00391-5 · Cited by 52 · see citing works
Self-citationInhibition of glutamate transporter by theanine enhances the therapeutic efficacy of doxorubicin
Sugiyama, T., Sadzuka, Y., Tanaka, K., & Sonobe, T. (2001) · Toxicology Letters · doi:10.1016/s0378-4274(01)00317-4 · Cited by 47 · see citing works
Self-citationGoto, T., Horie, H., & MUAKAI, T. (1993) · Chagyo Kenkyu Hokoku (Tea Research Journal) · doi:10.5979/cha.1993.29 · Cited by 33 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Muramatsu K., Oguni I., Isemura M., Sugiya- ma K., Yamamoto B. (ed.), ``Cha no Kinou,'' Gakkai Shuppan Center, Tokyo, 2002, pp. 1 416.
- Goto S., Horie H., Mukai T., ``Chagyo Kenkyu Hokoku,'' 77, 29 (1993).
- Sadzuka Y., Yamashita Y., Sonobe T., Clin. Cancer Res., in press.
Cited by
Sorted by citations
l -theanine: A potential multifaceted natural bioactive amide as health supplement
Adhikary, R., & Mandal, V. (2017) · Asian Pacific Journal of Tropical Biomedicine · doi:10.1016/j.apjtb.2017.08.005 · Cited by 55 · see citing works
L-theanine and immunity: a review
Chen, S., Kang, J., Zhu, H., Wang, K., Han, Z., Wang, L., Liu, J., Wu, Y., He, P., Tu, Y., et al. (2023) · Molecules · doi:10.3390/molecules28093846 · Cited by 44 · see citing works
Health Benefits of Theanine in Green Tea: A Review
Liang, Y.-R., Liu, C., Xiang, L.-P., & Zheng, X.-Q. (2015) · Tropical Journal of Pharmaceutical Research · doi:10.4314/tjpr.v14i10.29 · Cited by 31 · see citing works
- Authors
- SADZUKA, Y., YAMASHITA, Y., KISHIMOTO, S., FUKUSHIMA, S., TAKEUCHI, Y., & SONOBE, T.
- Affiliations
- Shizuoka University (JP)
- Kobe Gakuin University (JP)
- Venue
- YAKUGAKU ZASSHI
- Publisher
- Pharmaceutical Society of Japan
- Published
- 2002-11-01
- Volume
- 122
- Issue
- 11
- Pages
- 995-999
- ISSN
- 0031-6903 (ISSN-L)
- 1347-5231
- OpenAlex
- W2120261860
- Cited by
- 11
- References
- 11
- Citations by year
- 2023: 1 · 2020: 1 · 2017: 1 · 2015: 2 · 2012: 1
- FWCI
- 0.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- YAKUGAKU ZASSHI (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Medicine › Pathology and Forensic Medicine › Tea Polyphenols and Effects
- Keywords
- theanine, glutamate transporters, glutamate uptake inhibition, doxorubicin, cisplatin, irinotecan, glutathione conjugates, drug efflux, glutathione synthesis, anticancer activity, green tea, combination chemotherapy, tumor volume
- MeSH terms
- Irinotecan, Animals, Antineoplastic Agents, Camptothecin, Cisplatin, Depression, Chemical, Drug Synergism, Drug Therapy, Combination, Glutamates, Glutathione, Male, Neoplasm Transplantation, Sarcoma, Experimental, Tea, Tissue Distribution, Amino Acid Transport System X-AG, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
