Inner Mongolia University Research Center for Glycochemistry of Characteristic Medicinal Resources, Department of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot People's Republic of China, Inner Mongolia 010031, China.
Department of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, Pakistan.
Metallomics. 2022 Aug 8;14(8). doi: 10.1093/mtomcs/mfac053.
Vitamin B6 is an essential vitamin that serves as a co-enzyme in a number of enzymatic reactions in metabolism of lipids, amino acids, and glucose. In the current study, we synthesized vitamin B6 derived ligand (L) and its complex Pt(L)Cl (C1). The ancillary chloride ligand of C1 was exchanged with pyridine co-ligand and another complex Pt(L)(py).BF4 (C2) was obtained. Both these complexes were obtained in excellent isolated yields and characterized thoroughly by different analytical methods. Thyroid cancer is one of the most common malignancies of the endocrine system, we studied the in vitro anticancer activity and mechanism of these vitamin B6 derived L and Pt(II) complexes in thyroid cancer cell line (FTC). Based on MTT assay, cell proliferation rate was reduced in a dose-dependent manner. According to apoptosis analysis, vitamin B6 based Pt(II) complexes treated cells depicted necrotic effect and TUNEL based apoptosis was observed in cancer cells. Furthermore, qRT-PCR analyses of cancer cells treated with C1 and/or C2 showed regulated expression of anti-apoptotic, pro-apoptosis and autophagy related genes. Western blot results demonstrated that C1 and C2 induced the activation of p53 and the cleavage of Poly (ADP-ribose) polymerase (PARP). These results suggest that these complexes inhibit the growth of FTC cells and induce apoptosis through p53 signaling. Thus, vitamin B6 derived Pt(II) complexes C1 and C2 may be potential cytotoxic agents for the treatment of thyroid cancer.
维生素 B6 是一种必需维生素,作为许多代谢脂质、氨基酸和葡萄糖的酶反应中的辅酶。在目前的研究中,我们合成了维生素 B6 衍生的配体 (L) 及其配合物 Pt(L)Cl(C1)。C1 的辅助氯配体被吡啶共配体取代,得到另一个配合物 Pt(L)(py)。BF4(C2)。这两种配合物都以优异的分离产率获得,并通过不同的分析方法进行了彻底的表征。甲状腺癌是内分泌系统最常见的恶性肿瘤之一,我们研究了这些维生素 B6 衍生的 L 和 Pt(II)配合物在甲状腺癌细胞系 (FTC) 中的体外抗癌活性和机制。根据 MTT 测定,细胞增殖率呈剂量依赖性降低。根据凋亡分析,用维生素 B6 为基础的 Pt(II)配合物处理的细胞表现出坏死效应,并且在癌细胞中观察到 TUNEL 基于的凋亡。此外,用 C1 和/或 C2 处理的癌细胞的 qRT-PCR 分析显示抗凋亡、促凋亡和自噬相关基因的表达受到调节。Western blot 结果表明,C1 和 C2 诱导了 p53 的激活和多聚(ADP-核糖)聚合酶(PARP)的切割。这些结果表明,这些配合物通过 p53 信号抑制 FTC 细胞的生长并诱导细胞凋亡。因此,维生素 B6 衍生的 Pt(II)配合物 C1 和 C2 可能是治疗甲状腺癌的潜在细胞毒性药物。