Document Type

Article

Publication Date

2024

DOI

10.1002/pro.4867

Publication Title

Protein Science

Volume

33

Issue

3

Pages

e4867 (1-14)

Abstract

Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was conducted to quantitatively assess the binding of cisplatin to the protein, utilizing inductively coupled plasma-optical emission spectroscopy and atomic absorption spectroscopy. Our findings provide evidence of direct interaction between cl-Par-4 and cisplatin, and reveal a binding stoichiometry of 1:1. This result provides insights that could be useful in enhancing the efficacy of cisplatin-based and tumor suppressor-based cancer therapies.

Rights

© 2023 The Authors.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International (CC BY-NC-ND 4.0) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Original Publication Citation

Raut, K. K., Pandey, S., Kharel, G., & Pascal, S. M. (2024). Evidence of direct interaction between cisplatin and the caspase-cleaved prostate apoptosis response-4 tumor suppressor. Protein Science, 33(3), 1-14, Article e4867. https://doi.org/10.1002/pro.4867

ORCID

0000-0002-9492-6167 (Pascal)

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