Inhibition of Human APE1 and MTH1 DNA Repair Proteins by Dextran-Coated γ-Fe ₂ O ₃ Ultrasmall Superparamagnetic Iron Oxide Nanoparticles

Abstract

Aim: To quantitatively evaluate the inhibition of human DNA repair proteins APE1 and MTH1 by dextran-coated γ-Fe2O3 ultrasmall superparamagnetic iron oxide nanoparticles (dUSPIONs). Materials & methods: Liquid chromatography–tandem mass spectrometry with isotope-dilution was used to measure the expression levels of APE1 and MTH1 in MCL-5 cells exposed to increasing doses of dUSPIONs. The expression levels of APE1 and MTH1 were measured in cytoplasmic and nuclear fractions of cell extracts. Results: APE1 and MTH1 expression was significantly inhibited in both cell fractions at the highest dUSPION dose. The expression of MTH1 was linearly inhibited across the full dUSPION dose range in both fractions. Conclusion: These findings warrant further studies to characterize the capacity of dUSPIONs to inhibit other DNA repair proteins in vitro and in vivo.

Targeting MutT homolog 1 (MTH1) for breast cancer suppression by a novel MTH1 inhibitor MA-24 with tumor-selective toxicity

“…As a result, various types of MTH1 inhibitors have been developed, primarily classified as 2-aminopyrimidine derivatives, [19,20] (S)-crizotinib or pyrazoloquinoline derivatives, [21] natural extracts, [22,23] nucleoside analogs, [24] Kettle's three classes of inhibitors, [25] and nanoparticles. [26] All of these demonstrate a significant inhibitory effect on MTH1. In the present work, we report a novel MTH1 inhibitor, MA-24, which exhibits potent tumor-specific anti-breast cancer activity both in vitro and in vivo.…”

Targeting MutT Homolog 1 (MTH1) for Breast Cancer Suppression by Using a Novel MTH1 Inhibitor MA−24 with Tumor-Selective Toxicity

“…The inhibition of MTH1 can exert anticancer effects by preserving normal cell viability and exhibits broad-spectrum anticancer activity; TH287 and TH588 are the first small-molecule inhibitors targeting MTH1, and their potent anticancer effects have sparked interest in MTH1 inhibitors among researchers [ 8 ]. As a result, various types of MTH1 inhibitors have been developed, primarily classified as 2-aminopyrimidine derivatives [ 19 , 20 ], (S)-crizotinib or pyrazoloquinoline derivatives [ 21 ], natural extracts [ 22 , 23 ], nucleoside analogs [ 24 ], Kettle’s three classes of inhibitors [ 25 ], and nanoparticles [ 26 ]. All of these demonstrate a significant inhibitory effect on MTH1.…”