Department of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, Chennai 603 203, Tamil Nadu, India.
Department of Molecular Medicine, School of Allied Healthcare and Sciences, Jain Deemed-to-be University, Bangalore 560 066, Karnataka, India.
Molecules. 2022 Oct 28;27(21):7333. doi: 10.3390/molecules27217333.
In this study, the anti-cancer and anti-inflammatory activities of PS14, a short peptide derived from the cellulase binding domain of pathogenic fungus, , have been evaluated, in vitro and in vivo. Bioinformatics analysis of PS14 revealed the physicochemical properties and the web-based predictions, which indicate that PS14 is non-toxic, and it has the potential to elicit anti-cancer and anti-inflammatory activities. These in silico results were experimentally validated through in vitro (L6 or Hep-2 cells) and in vivo (zebrafish embryo or larvae) models. Experimental results showed that PS14 is non-toxic in L6 cells and the zebrafish embryo, and it elicits an antitumor effect Hep-2 cells and zebrafish embryos. Anticancer activity assays, in terms of MTT, trypan blue and LDH assays, showed a dose-dependent inhibitory effect on cell proliferation. Moreover, in the epithelial cancer cells and zebrafish embryos, the peptide challenge (i) caused significant changes in the cytomorphology and induced apoptosis; (ii) triggered ROS generation; and (iii) showed a significant up-regulation of anti-cancer genes including BAX, Caspase 3, Caspase 9 and down-regulation of Bcl-2, in vitro. The anti-inflammatory activity of PS14 was observed in the cell-free in vitro assays for the inhibition of proteinase and lipoxygenase, and heat-induced hemolysis and hypotonicity-induced hemolysis. Together, this study has identified that PS14 has anti-cancer and anti-inflammatory activities, while being non-toxic, in vitro and in vivo. Future experiments can focus on the clinical or pharmacodynamics aspects of PS14.
在这项研究中,评估了来源于致病真菌纤维素结合域的短肽 PS14 的体外和体内抗癌和抗炎活性。PS14 的生物信息学分析揭示了理化性质和基于网络的预测,表明 PS14 无毒,并且具有引发抗癌和抗炎活性的潜力。这些计算机模拟结果通过体外(L6 或 Hep-2 细胞)和体内(斑马鱼胚胎或幼虫)模型得到了实验验证。实验结果表明,PS14 在 L6 细胞和斑马鱼胚胎中无毒,在 Hep-2 细胞和斑马鱼胚胎中具有抗肿瘤作用。抗癌活性测定(MTT、台盼蓝和 LDH 测定)表明,该肽对细胞增殖具有剂量依赖性抑制作用。此外,在上皮癌细胞和斑马鱼胚胎中,肽的挑战(i)导致细胞形态发生明显变化并诱导细胞凋亡;(ii)触发 ROS 生成;并且(iii)在体外显著上调了抗癌基因,包括 BAX、Caspase 3、Caspase 9,并下调了 Bcl-2。PS14 的抗炎活性在体外无细胞蛋白酶和脂氧合酶抑制、热诱导溶血和低渗诱导溶血测定中观察到。总之,这项研究表明 PS14 具有体外和体内的抗癌和抗炎活性,同时无毒。未来的实验可以集中在 PS14 的临床或药效学方面。