Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington, TX, 76019, United States.
Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington, TX, 76019, United States.
J Pharm Biomed Anal. 2019 Feb 5;164:421-429. doi: 10.1016/j.jpba.2018.10.047. Epub 2018 Oct 28.
Herein we describe for the first time the endogenous levels of free l-and d-amino acids in cultured human breast cancer cells (MCF-7) and non-tumorigenic human breast epithelial cells (MCF-10A). d-Asp and d-Ser, which are co-agonists of the N-methyl-d-aspartate (NMDA) receptors, showed significantly elevated levels in MCF-7 cancer cells compared to MCF-10A cells. This may result from upregulated enzymatic racemases. Possible roles of these d-amino acids in promoting breast cancer proliferation by regulating NMDA receptors were indicated. d-Asn may also be able to serve as exchange currency, like specific l-amino acids, for the required uptake of essential amino acids and other low abundance nonessential amino acids which were elevated nearly 60 fold in cancer cells. The relative levels of specific l- and d-amino acids can be used as malignancy indicators (MIs) for the breast cancer cell line in this study. High MIs (>50) result from the increased demands of specific essential amino acids. Very low MIs (<1) result from the increased demands of specific d-amino acids (i.e., d-Ser, d-Asp) or the cellular release of amino acid exchange currency (i.e., l- and d-Asn) used in the upregulated amino acid antiporters to promote cancer cell proliferation.
在此，我们首次描述了培养的人乳腺癌细胞（MCF-7）和非致瘤性人乳腺上皮细胞（MCF-10A）中游离 l-和 d-氨基酸的内源性水平。d-Asp 和 d-Ser 是 N-甲基-d-天冬氨酸（NMDA）受体的共激动剂，与 MCF-10A 细胞相比，MCF-7 癌细胞中的水平显著升高。这可能是由于酶促消旋酶的上调所致。这些 d-氨基酸可能通过调节 NMDA 受体在促进乳腺癌增殖方面发挥作用。d-Asn 也可能能够像特定的 l-氨基酸一样，作为交换货币，用于必需氨基酸和其他低丰度非必需氨基酸的必需摄取，这些氨基酸在癌细胞中的含量增加了近 60 倍。特定的 l-和 d-氨基酸的相对水平可以用作本研究中乳腺癌细胞系的恶性指标 (MI)。高 MI (>50) 是由于特定必需氨基酸的需求增加所致。非常低的 MI (<1) 是由于特定 d-氨基酸（即 d-Ser、d-Asp）的需求增加或氨基酸交换货币（即 l-和 d-Asn）的细胞释放所致，这些货币用于上调的氨基酸转运蛋白以促进癌细胞增殖。
