JPH203, an L-Type Amino Acid Transporter 1-Selective Compound, Induces Apoptosis of YD-38 Human Oral Cancer Cells
JPH203, an L-Type Amino Acid Transporter 1-Selective Compound, Induces Apoptosis of YD-38 Human Oral Cancer Cells
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DOI：
10.1254/jphs.13154fp
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发表时间：
2014-02-01
影响因子：
3.5
通讯作者：
Kim, Do Kyung
中科院分区：
文献类型：
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作者：
Yun, Dae-Woong;Lee, Seul Ah;Kim, Do Kyung
与大多数表达l型氨基酸转运蛋白2的正常细胞相比，l型氨基酸转运蛋白1在癌细胞中高度表达，并被认为支持其加速生长和增殖。本研究检测了强效、选择性的l型氨基酸转运蛋白1抑制剂JPH203对人口腔癌YD-38细胞生长的抑制能力。YD-38细胞表达l型氨基酸转运蛋白1及其相关蛋白4F2重链，但不表达l型氨基酸转运蛋白2。JPH203和非选择性l型氨基酸转运蛋白抑制剂BCH完全抑制了ld -38细胞对l -亮氨酸的摄取。正如预期的那样，JPH203抑制l -亮氨酸摄取的内在亲和力远比BCH有效。同样，JPH203和BCH对YD-38细胞的生长也有抑制作用，且JPH203的抑制作用优于BCH。JPH203通过激活caspases、PARP等凋亡因子，上调pd -38细胞的凋亡数量。这些结果表明，JPH203对l型氨基酸转运蛋白1活性的抑制，可能作为一种潜在的新型抗口腔癌药物，通过诱导细胞内癌细胞生长必需的中性氨基酸的耗竭，导致YD-38口腔癌细胞凋亡。
Compared to most normal cells that express L-type amino acid transporter 2, L-type amino acid transporter 1 is highly expressed in cancer cells and presumed to support their elevated growth and proliferation. This study examined JPH203, a potent and selective L-type amino acid transporter 1 inhibitor, and its ability to suppress YD-38 human oral cancer cell growth. The YD-38 cells express L-type amino acid transporter 1 with its associating protein 4F2 heavy chain, but not L-type amino acid transporter 2. JPH203 and BCH, a non-selective L-type amino acid transporter inhibitor, completely inhibited L-leucine uptake in YD-38 cells. As expected, the intrinsic affinity of JPH203 to inhibit L-leucine uptake was far more efficient than BCH. Likewise, JPH203 and BCH inhibited YD-38 cell growth, with JPH203 being superior to BCH. JPH203 up-regulated the population of apoptotic YD-38 cells through the activation of apoptotic factors, including caspases and PARP. These results suggest that the inhibition of L-type amino acid transporter 1 activity via JPH203, which may act as a potential novel anti oral-cancer agent, leads to apoptosis by inducing the intracellular depletion of the neutral amino acids essential for cancer cell growth in YD-38 human oral cancer cells.