Issue 2, 2022

Designed hybrid anticancer nuclear-localized peptide inhibits aggressive cancer cell proliferation

Abstract

Cell proliferation is a crucial step that might promote cancer if deregulated. Therefore, this vital segment is critically controlled by a complicated cell-cycle process in normal cells that is regulated by some regulatory proteins. It has been observed that p16 protein, playing a crucial role in cell-cycle progression/regulation, remains inactivated in different cancer cells. This inactivity of p16 protein leads to the enhancement of cancer cell proliferation by allowing uncontrolled cancer cell division. Hence, the activity of p16 protein needs to be restored using new viral vectors, small molecules as well as peptides to control/suppress this type of abnormal cell proliferation. In this work, we have taken an interesting approach to increase the efficiency and bio-availability of p16 peptide (functional part of p16 protein) to be an aggressive anti-leukemia therapeutic agent by conjugating a nuclear-localized signal (NLS) sequence and a short peptide (AVPI) with it. Moreover, this newly designed NLS attached hybrid peptide greatly affects XIAP expressing but p16 lower expressing human chronic myelogenous leukemia (CML) cell proliferation by targeting both nuclear (CDK4/cyclin D) and cellular factors (XIAP) and promoting the caspase-3 dependent apoptosis pathway.

Graphical abstract: Designed hybrid anticancer nuclear-localized peptide inhibits aggressive cancer cell proliferation

Supplementary files

Article information

Article type
Research Article
Submitted
06 Oct 2021
Accepted
16 Dec 2021
First published
23 Dec 2021

RSC Med. Chem., 2022,13, 196-201

Designed hybrid anticancer nuclear-localized peptide inhibits aggressive cancer cell proliferation

P. Mondal, S. Mohapatra, D. Bhunia, P. K. Gharai, N. Mukherjee, V. Gupta, S. Ghosh and S. Ghosh, RSC Med. Chem., 2022, 13, 196 DOI: 10.1039/D1MD00324K

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