Department of Cellular and Molecular Biology, Faculty of Basic Science, Imam Hossein University, Tehran, Iran.
Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran.
Arch Microbiol. 2023 May 6;205(6):220. doi: 10.1007/s00203-023-03563-3.
Targeted delivery of a toxin substance to cancer cells is one of the most recent cancer treatment options. Mistletoe Lectin-1 (ML1) in Viscum album L. is a Ribosome-inactivating proteins with anticancer properties. Therefore, it appears that a recombinant protein with selective permeability can be generated by fusing ML1 protein with Shiga toxin B, which can bind to Gb3 receptor that is abundantly expressed on cancer cells. In this study, we sought to produce and purify a fusion protein containing ML1 fused to STxB and evaluate its cytotoxic activities. The ML1-STxB fusion protein coding sequence was cloned into the pET28a plasmid, then was transformed into E. coli BL21-DE3 cells. Following induction of protein expression, Ni-NTA affinity chromatography was used to purify the protein. Using SDS-PAGE and western blotting, the expression and purification processes were validated. On the SkBr3 cell line, the cytotoxic effects of the recombinant proteins were evaluated. On SDS-PAGE and western blotting membrane, analysis of purified proteins revealed a band of approximately 41 kDa for rML1-STxB. Ultimately, statistical analysis demonstrated that rML1-STxB exerted significant cytotoxic effects on SkBr3 cells at 18.09 and 22.52 ng/L. The production, purification, and encapsulation of rML1-STxB fusion protein with potential cancer cell-specific toxicity were successful. However, additional research must be conducted on the cytotoxic effects of this fusion protein on other malignant cell lines and in vivo cancer models.
将毒素物质靶向递送到癌细胞是最近的癌症治疗选择之一。槲寄生凝集素-1(ML1)在欧洲白蜡树中是一种核糖体失活蛋白,具有抗癌特性。因此,似乎可以通过将 ML1 蛋白与志贺毒素 B 融合来产生具有选择性通透性的重组蛋白,后者可以与在癌细胞上大量表达的 Gb3 受体结合。在这项研究中,我们试图生产和纯化含有 ML1 融合到 STxB 的融合蛋白,并评估其细胞毒性活性。将 ML1-STxB 融合蛋白编码序列克隆到 pET28a 质粒中,然后转化到 E. coli BL21-DE3 细胞中。在诱导蛋白表达后,使用 Ni-NTA 亲和层析纯化蛋白。使用 SDS-PAGE 和 Western blot 验证表达和纯化过程。在 SkBr3 细胞系上评估重组蛋白的细胞毒性作用。在 SDS-PAGE 和 Western blot 膜上,对纯化蛋白的分析显示 rML1-STxB 的约 41 kDa 带。最终,统计分析表明 rML1-STxB 在 18.09 和 22.52 ng/L 时对 SkBr3 细胞具有显著的细胞毒性作用。rML1-STxB 融合蛋白的生产、纯化和封装具有潜在的癌细胞特异性毒性已成功完成。然而,必须在其他恶性细胞系和体内癌症模型上进一步研究该融合蛋白的细胞毒性作用。