Fatima Syeda Warisul, Imtiyaz Khalid, Alam Rizvi Mohammad M, Khare Sunil K
Enzyme and Microbial Biochemistry Laboratory, Department of Chemistry, Indian Institute of Technology Delhi New Delhi-110016 India
Genome Biology Laboratory, Department of Biosciences, Jamia Millia Islamia New Delhi-110025 India.
RSC Adv. 2021 Oct 26;11(55):34613-34630. doi: 10.1039/d1ra04513j. eCollection 2021 Oct 25.
Breast cancer is the most common malignancy among women. With the aim of decreasing the toxicity of conventional breast cancer treatments, an alternative that could provide appropriate and effective drug utilization was envisioned. Thus, we contemplated and compared the effects of microbial transglutaminase nanoflowers (MTGase NFs) on breast cancer cells (MCF-7). Transglutaminase is an important regulatory enzyme acting as a site-specific cross-linker for proteins. With the versatility of MTGase facilitating the nanoflower formation by acting as molecular glue, it was demonstrated to have anti-cancer properties. The rational drug design based on a transglutaminase enzyme-assisted approach led to the uniform shape of petals in these nanoflowers, which had the capacity to act directly as an anti-cancer drug. Herein, we report the anti-cancer characteristics portrayed by enzymatic MTGase NFs, which are biocompatible in nature. This study demonstrated the prognostic and therapeutic significance of MTGase NFs as a nano-drug in breast cancer treatment. The results on MCF-7 cells showed a significantly improved therapeutic efficacy. MTGase NFs were able to exhibit inhibitory effects on cell viability (IC-8.23 μg ml) within 24 h of dosage. To further substantiate its superior anti-proliferative role, the clonogenic potential was measured to be 62.8%, along with migratory inhibition of cells (3.76-fold change). Drastic perturbations were induced (4.61-fold increase in G0/G1 phase arrest), pointed towards apoptotic induction with a 58.9% effect. These results validated the role of MTGase NFs possessing a cytotoxic nature in mitigating breast cancer. Thus, MTGase bestows distinct functionality towards therapeutic nano-modality, nanoflowers, which shows promise in cancer treatment.
乳腺癌是女性中最常见的恶性肿瘤。为了降低传统乳腺癌治疗的毒性，人们设想了一种能够实现适当且有效药物利用的替代方法。因此，我们思考并比较了微生物转谷氨酰胺酶纳米花（MTGase NFs）对乳腺癌细胞（MCF - 7）的影响。转谷氨酰胺酶是一种重要的调节酶，可作为蛋白质的位点特异性交联剂。MTGase具有多功能性，通过充当分子胶水促进纳米花的形成，已证明其具有抗癌特性。基于转谷氨酰胺酶辅助方法的合理药物设计导致这些纳米花具有均匀的花瓣形状，能够直接作为抗癌药物发挥作用。在此，我们报告了酶促MTGase NFs所呈现的抗癌特性，其本质上具有生物相容性。本研究证明了MTGase NFs作为纳米药物在乳腺癌治疗中的预后和治疗意义。对MCF - 7细胞的研究结果显示治疗效果显著提高。MTGase NFs在给药24小时内能够对细胞活力表现出抑制作用（IC - 8.23 μg/ml）。为了进一步证实其卓越的抗增殖作用，克隆形成潜力测定为62.8%，同时细胞迁移受到抑制（变化3.76倍）。诱导了剧烈的扰动（G0/G1期阻滞增加4.61倍），表明凋亡诱导率为58.9%。这些结果证实了具有细胞毒性的MTGase NFs在减轻乳腺癌方面的作用。因此，MTGase赋予了治疗性纳米形态——纳米花独特的功能，在癌症治疗中显示出前景。
