Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 St., 30-688 Cracow, Poland.
Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, św. Łazarza 16 St., 31-530 Cracow, Poland.
Int J Mol Sci. 2023 Feb 14;24(4):3788. doi: 10.3390/ijms24043788.
Cancer cells are characterized by uncontrolled growth, proliferation, and impaired apoptosis. Tumour progression could be related to poor prognosis and due to this fact, researchers have been working on novel therapeutic strategies and antineoplastic agents. It is known that altered expression and function of solute carrier proteins from the SLC6 family could be associated with severe diseases, including cancers. These proteins were noticed to play important physiological roles through transferring nutrient amino acids, osmolytes, neurotransmitters, and ions, and many of them are necessary for survival of the cells. Herein, we present the potential role of taurine (SLC6A6) and creatine (SLC6A8) transporters in cancer development as well as therapeutic potential of their inhibitors. Experimental data indicate that overexpression of analyzed proteins could be connected with colon or breast cancers, which are the most common types of cancers. The pool of known inhibitors of these transporters is limited; however, one ligand of SLC6A8 protein is currently tested in the first phase of clinical trials. Therefore, we also highlight structural aspects useful for ligand development. In this review, we discuss SLC6A6 and SLC6A8 transporters as potential biological targets for anticancer agents.
癌细胞的特征是不受控制的生长、增殖和凋亡受损。肿瘤的进展可能与预后不良有关,基于这一事实,研究人员一直在研究新的治疗策略和抗肿瘤药物。已知 SLC6 家族溶质载体蛋白的表达和功能改变可能与包括癌症在内的严重疾病有关。这些蛋白通过转运营养氨基酸、渗透物、神经递质和离子,发挥着重要的生理作用,其中许多对于细胞的生存是必需的。在此,我们介绍了牛磺酸(SLC6A6)和肌氨酸(SLC6A8)转运蛋白在癌症发展中的潜在作用,以及它们抑制剂的治疗潜力。实验数据表明,分析蛋白的过表达可能与最常见的两种癌症——结肠癌和乳腺癌有关。这些转运蛋白的已知抑制剂数量有限;然而,SLC6A8 蛋白的一种配体目前正在临床试验的第一阶段进行测试。因此,我们还强调了对配体开发有用的结构方面。在这篇综述中,我们讨论了 SLC6A6 和 SLC6A8 转运蛋白作为抗癌药物的潜在生物靶标。