4-Methylthiazole Triggers Apoptosis and Mitochondrial Disruption in HL-60 Cells

Author:

Meriç Neslihan1,Kar Ezgi1,Kar Fatih1

Affiliation:

1. Kütahya Sağlık Bilimleri Üniversitesi

Abstract

Abstract

Thiazole derivatives are gaining prominence in cancer research due to their potent anti-cancer effects and multifaceted biological activities. Notably, in leukemia research, these compounds are studied for their ability to induce apoptosis, disrupt mitochondrial membrane potential (MMP), and modulate cell signaling pathways. This study focuses on 4-Methylthiazole's effectiveness in inducing apoptosis in HL-60 leukemia cells. It significantly disrupts MMP, activates caspase-3, and promotes cytochrome c release, which are key indicators of apoptosis (**** p < 0.0001, *** p < 0.001, ** p < 0.01, * p < 0.05). Additionally, 4-Methylthiazole reduces CD45 and CD123 surface markers, altering the phenotypic characteristics of leukemia cells (**** p < 0.0001). A high-dose treatment with 4-Methylthiazole significantly increases ROS levels, pointing to elevated oxidative stress and intracellular free radicals, contributing to its cytotoxic effects (*p < 0.05). The study also observed a significant rise in TNF-α levels post-treatment, indicating a pro-inflammatory response that may further inhibit leukemia cell viability. While IL-6 levels remained unchanged, a dose-dependent decrease in IL-10 levels was noted, suggesting a reduction in immunosuppressive conditions within the tumor microenvironment (*p < 0.05). Overall, 4-Methylthiazole targets leukemia cells through multiple apoptotic mechanisms and modifies the immune landscape of the tumor microenvironment, enhancing its therapeutic potential. This study highlights the need for further clinical investigation to fully exploit the potential of thiazole derivatives in leukemia treatment.

Publisher

Springer Science and Business Media LLC

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