Inhibition of oligopeptide transporter suppress growth of human pancreatic cancer cells
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Abstract
金沢大学医薬保健研究域薬学系
Oligopeptide transporters are abundantly expressed in various types of cancer cells. We here synthesized two novel dipeptides, l-phenylalanyl sarcosine (Phe-Sar) and 4-(4-methoxyphenyl)-l-phenylalanyl sarcosine (Bip(OMe)-Sar), and examined their effect on the growth of human pancreatic cancer AsPC-1 cells, which are known to highly express oligopeptide transporter PEPT1/SLC15A1. Growth of AsPC-1 cells was inhibited by these two peptides and a typical PEPT1/SLC15A1 substrate Gly-Sar. Growth inhibition by Gly-Sar, Phe-Sar and Bip(OMe)-Sar was concentration-dependent with half-maximal inhibitory concentration of 50, 0.91 and 0.55mM, respectively. These peptides also inhibited PEPT1-mediated [3H]Gly-Sar uptake with half-maximal inhibitory concentration of 2.6, 0.81 and 0.27mM, respectively. Thus, the rank order of the tumor cell growth inhibition by these three peptides was the same as that of PEPT1-inhibitory activity. Growth of AsPC-1 cells was also inhibited by 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid (BCH), which is a typical inhibitor of amino acid transporter system L. The growth inhibition by BCH and Gly-Sar was additive, suggesting that these compounds act at distinct loci. Oligopeptide transporters thus appear to be a promising target for inhibition of pancreatic cancer progression. These results also proposed the idea that oligopeptide transporter is required for growth of AsPC-1 cells. © 2010 Elsevier B.V.
Journal
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- European Journal of Pharmaceutical Sciences
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European Journal of Pharmaceutical Sciences 40 (3), 202-208, 2010-06-01
Elsevier BV
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Details 詳細情報について
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- CRID
- 1050845760884188416
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- NII Article ID
- 120002224386
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- NII Book ID
- AA10934504
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- ISSN
- 09280987
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- Web Site
- http://hdl.handle.net/2297/24628
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- CiNii Articles