The Thioredoxin-1 Inhibitor, PX-12, Suppresses Local Osteosarcoma Progression.

Abstract

BACKGROUND/AIM:

The thioredoxin-1 (Trx-1) inhibitor, PX-12, is active against several cancer types. This study aimed to evaluate its effects on local osteosarcoma (OS) progression and to describe PX-12-related signal transduction pathways.

MATERIALS AND METHODS:

Publicly available expression cohort data were analyzed to determine the relationship between the expression levels of TXN, which codes for the Trx protein, and survival in patients with OS. Murine LM8 OS cells were stimulated with PX-12. Apoptosis-related protein levels, cell viability, caspase activity, and wound healing were evaluated. PX-12 efficacy in suppressing tumor progression was evaluated in C3H mice injected with LM8 cells.

RESULTS:

High TXN expression was a negative prognostic factor for metastasis and overall survival in OS patients. PX-12 induced apoptosis in OS cells via the oxidative stress-MAPK-caspase 3 pathway and suppressed OS cell migration. PX-12 suppressed local OS progression.

CONCLUSION:

PX-12 is a potential therapeutic agent for use in suppressing local OS progression.

• Authors: Hideyuki Kinoshita, Osamu Shimozato, Takeshi Ishii, Hiroto Kamoda, Yoko Hagiwara, Seiji Ohtori, Tsukasa Yonemoto
• Journal: Anticancer research (Anticancer Res) Vol. 41 Issue 12 Pg. 6013-6021 (Dec 2021) ISSN: 1791-7530 [Electronic] Greece
• PMID: 34848455 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Antineoplastic Agents
• Disulfides
• Imidazoles
• TXN protein, human
• Thioredoxins
• 1-methylpropyl-2-imidazolyl disulfide

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Disease Models, Animal
• Disease Progression
• Disulfides (pharmacology)
• Dose-Response Relationship, Drug
• Humans
• Imidazoles (pharmacology)
• Mice
• Oxidative Stress (drug effects)
• Thioredoxins (antagonists & inhibitors)
• Xenograft Model Antitumor Assays