Postu Paula Alexandra, Boiangiu Razvan Stefan, Mihasan Marius, Stache Alexandru Bogdan, Tiron Adrian, Hritcu Lucian
Center for Fundamental Research and Experimental Development in Translation Medicine-TRANSCEND, Regional Institute of Oncology, 700483 Iasi, Romania.
Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University of Iasi, 700506 Iasi, Romania.
Molecules. 2024 Nov 26;29(23):5593. doi: 10.3390/molecules29235593.
6-hydroxy-L-nicotine (6HLN) is a nicotine (NIC) derivative with proven therapeutic potential in neurodegenerative disorders. Here, the impact of 6HLN on cell growth, migratory behavior, and inflammatory status of three different cancer cell lines (A549, MCF7, and U87) and two normal cell lines (16HBE14o and MCF10A) was investigated. In silico analyses were conducted to evaluate the binding affinity of 6HLN to nicotinic receptors (nAChRs) containing α9 and α5 subunits. The obtained in silico data revealed that 6HLN might act on the cholinergic system. Interestingly, the in vitro data showed the compound has cancer-stimulatory effects in U87 glioblastoma cells and cancer-inhibitory effects in MCF7 breast cancer cells. In A549 lung cancer cells, no changes were detected upon 6HLN administration. More importantly, 6HLN appears not to be deleterious for normal cells, with the viability of 16HBE14o pulmonary cells and MCF10A mammary cells remaining unchanged.
6-羟基-L-尼古丁（6HLN）是一种尼古丁（NIC）衍生物，在神经退行性疾病中具有已被证实的治疗潜力。在此，研究了6HLN对三种不同癌细胞系（A549、MCF7和U87）以及两种正常细胞系（16HBE14o和MCF10A）的细胞生长、迁移行为和炎症状态的影响。进行了计算机模拟分析，以评估6HLN对含有α9和α5亚基的烟碱受体（nAChRs）的结合亲和力。获得的计算机模拟数据显示，6HLN可能作用于胆碱能系统。有趣的是，体外数据表明该化合物对U87胶质母细胞瘤细胞具有癌症刺激作用，对MCF7乳腺癌细胞具有癌症抑制作用。在A549肺癌细胞中，给予6HLN后未检测到变化。更重要的是，6HLN似乎对正常细胞无害，16HBE14o肺细胞和MCF10A乳腺细胞的活力保持不变。
