CDC25B Inhibition by Menadione: A Potential New Therapeutical Approach

Abstract

Gastric cancer (GC) is the fifth most common type of tumor and the third leading cause of cancer death worldwide. The evolution of gastric carcinogenesis is still poorly understood and, for this reason, preclinical research protocols were established that included the development of gastric cancer cell lines and the establishment of models of gastric carcinogenesis in non-human primate Sapajus apella. A comprehensive literature search was performed in relevant databases such as PubMed, ResearchGate and Google Scholar to identify studies related to the topic. After an in-depth study of these reports, significant data/data were collected and compiled under appropriate headings. The main result of the studies carried out by the group on GC is the demonstration of the MYC gene overexpression as a common phenomenon in stomach carcinogenesis. Furthermore, we revealed that reducing the expression of the CDC25B gene, regulated by the MYC protein, is a therapeutic strategy against stomach tumors. This review article reveals preclinical evidence that treatment with menadione in experimental models of gastric tumorigenesis, in vivo and in vitro, inhibits the action of the phosphatase CDC25B and, consequently, prevents cell proliferation, invasion and migration.

Shikonin and Juglone Inhibit Mycobacterium tuberculosis Low-Molecular-Weight Protein Tyrosine Phosphatase a (Mt-PTPa)

“…The findings reported in this study show that naphthoquinones could be a group of compounds with specific allosteric inhibitory effects on the Mycobacterium tuberculosis protein tyrosine phosphatase A. Ribiero et al [ 50 ] reviewed the potential for developing CDC25 inhibition via the naphthoquinone menadione for therapeutic applications. Yoshikawa et al [ 51 ] showed that menadione inhibits another PTP, PTEN, both in vitro and in vivo.…”

“…The estimated IC 50 values are shown in Table 1. Among these, shikonin showed strong inhibition (IC 50 33 µM) at a concentration that is potentially clinically relevant. This is consistent with reports in the literature of the inhibition of other protein tyrosine phosphatases via shikonin.…”