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Novel Mannich base 3FB3FA8H induces apoptosis by upregulating P53 pathway in neuroblastoma cells

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Abstract

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.

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Authors and Affiliations

  1. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Syed Saad Hussain, Shaheen Faizi & Shabana U. Simjee

  2. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Kinza Rafi & Shabana U. Simjee

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  1. Syed Saad Hussain
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  2. Shaheen Faizi
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Hussain, S.S., Faizi, S., Rafi, K. et al. Novel Mannich base 3FB3FA8H induces apoptosis by upregulating P53 pathway in neuroblastoma cells. Mol Cell Biochem 471, 29–39 (2020). https://doi.org/10.1007/s11010-020-03755-1

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