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Novel Mannich base 3FB3FA8H induces apoptosis by upregulating P53 pathway in neuroblastoma cells.
Molecular and Cellular Biochemistry ( IF 3.5 ) Pub Date : 2020-05-29 , DOI: 10.1007/s11010-020-03755-1
Syed Saad Hussain 1 , Shaheen Faizi 1 , Kinza Rafi 2 , Shabana U Simjee 1, 2
Affiliation  

P53 plays an important role in maintaining genetic stability and development of resistance against tumors. Dysregulation of P53 gene is one of the key factors contributing to the etiology of neuroblastoma which causes cells to evade apoptosis. Activating P53 pathway can be a therapeutic alternative to the currently available medicinal strategies. Mannich bases have been known to possess various biological activities including the anticancer activity. In this study, we have targeted the P53 pathway by novel Mannich base (3FB3FA8H) which can be a future prospect to cure neuroblastoma. 3FB3FA8H has shown modulation of P53 pathway leading to apoptosis of neuroblastoma cells. Mitochondrial membrane permeability is also increased by 3FB3FA8H which may be a consequence of P53 pathway modulation. 3FB3FA8H increases the mRNA levels of P53 leading to activation of BAX. Inclining BAX/BCL2 ratio towards apoptotic BAX leads to cleavage of caspase 3, ultimately, causing apoptosis. Series of experiments provide the evidence that Mannich base 3FB3FA8H leads to P53-mediated apoptosis. Inducing apoptosis by this mechanism could be of central importance in reducing tumor burden which can be a good prospect for neuroblastoma patients.



中文翻译:

新型曼尼希碱基3FB3FA8H通过上调神经母细胞瘤细胞中的P53途径诱导凋亡。

P53在维持遗传稳定性和发展抗肿瘤性方面起着重要作用。P53基因的失调是促成神经母细胞瘤病因的关键因素之一,它可导致细胞逃避凋亡。激活P53途径可以替代当前可用的药物治疗策略。已知曼尼希碱具有多种生物活性,包括抗癌活性。在这项研究中,我们已针对新型Mannich碱基(3FB3FA8H)靶向P53途径,这可能是治疗神经母细胞瘤的未来前景。3FB3FA8H已显示出对P53通路的调节,导致神经母细胞瘤细胞凋亡。3FB3FA8H也增加了线粒体膜的通透性,这可能是P53途径调节的结果。3FB3FA8H增加P53的mRNA水平,从而激活BAX。BAX / BCL2比例朝着凋亡BAX倾斜会导致caspase 3裂解,最终导致细胞凋亡。系列实验提供了曼尼希碱基3FB3FA8H导致P53介导的细胞凋亡的证据。通过这种机制诱导细胞凋亡在减少肿瘤负担中可能是至关重要的,这对于神经母细胞瘤患者来说是一个很好的前景。

更新日期:2020-05-29
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