Targeting Polo-like Kinase 1 by a Novel Pyrrole-Imidazole Polyamide-Hoechst Conjugate Suppresses Tumor Growth In Vivo

Molecular Cancer Therapeutics
Ke LiuHongchang Li

Abstract

The serine/threonine kinase Polo-like kinase 1 (Plk1) plays a pivotal role in cell proliferation and has been validated as a promising anticancer drug target. However, very limited success has been achieved in clinical applications using existing Plk1 inhibitors, due to lack of sufficient specificity toward Plk1. To develop a novel Plk1 inhibitor with high selectivity and efficacy, we designed and synthesized a pyrrole-imidazole polyamide-Hoechst conjugate, PIP3, targeted to specific DNA sequence in the PLK1 promoter. PIP3 could specifically inhibit the cell cycle-regulated Plk1 expression and consequently retard tumor cell growth. Cancer cells treated with PIP3 exhibited severe mitotic defects and increased apoptosis, whereas normal cells were not affected by PIP3 treatment. Furthermore, subcutaneous injection of PIP3 into mice bearing human cancer xenografts induced significant tumor growth suppression with low host toxicity. Therefore, PIP3 exhibits the potential as an effective agent for targeted cancer therapy. Mol Cancer Ther; 17(5); 988-1002. ©2018 AACR.

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Citations

Oct 20, 2018·The Journal of Craniofacial Surgery·Jaime Castro-Núñez
Dec 31, 2020·Cancer Science·Sakthisri KrishnamurthyHiroki Nagase
Jul 31, 2021·Biochemical and Biophysical Research Communications·Meiqing LiWu Su
Feb 12, 2019·Advanced Drug Delivery Reviews·Zutao YuHiroshi Sugiyama

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