Faculty of Engineering and Natural Sciences, Department of Molecular Biology and Genetics, Kütahya Health Sciences University, Kütahya, Turkey.
Faculty of Health Sciences, Department of Nutrition and Dietetics, Kütahya Health Sciences University, Kütahya, Turkey.
Mol Biol Rep. 2024 Sep 19;51(1):997. doi: 10.1007/s11033-024-09939-y.
Thiazole derivatives are gaining prominence in cancer research due to their potent anti-cancer effects and multifaceted biological activities. In leukemia research, these compounds are particularly studied for their ability to induce apoptosis, disrupt mitochondrial membrane potential (MMP), and modulate cell signaling pathways.
This study investigates the efficacy of 4-Methylthiazole in inducing apoptosis in HL-60 leukemia cells. Apoptosis was quantified via flow cytometry using FITC Annexin V and propidium iodide staining. Mitochondrial disruption was evaluated through alterations in mitochondrial membrane potential (MMP) as measured by the JC-1 assay. The compound significantly disrupted MMP, activated Caspase-3, and induced the release of Cytochrome C, all of which are critical markers of apoptosis (****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05). Additionally, treatment with 4-Methylthiazole markedly reduced CD45 and CD123 surface markers, indicating significant phenotypic alterations in leukemia cells (****p < 0.0001). High-dose treatment with 4-Methylthiazole significantly increased ROS levels, suggesting elevated oxidative stress and the presence of intracellular free radicals, contributing to its cytotoxic effects (*p < 0.05). A significant rise in TNF-α levels was observed 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.
噻唑衍生物因其强大的抗癌作用和多方面的生物活性，在癌症研究中备受关注。在白血病研究中，这些化合物因其诱导细胞凋亡、破坏线粒体膜电位（MMP）和调节细胞信号通路的能力而受到特别研究。
本研究调查了 4-甲基噻唑在诱导 HL-60 白血病细胞凋亡中的功效。通过使用 FITC 膜联蛋白 V 和碘化丙啶染色的流式细胞术定量细胞凋亡。通过 JC-1 测定评估线粒体破坏，即通过测量线粒体膜电位（MMP）的变化来评估线粒体破坏。该化合物显著破坏 MMP，激活 Caspase-3，并诱导细胞色素 C 的释放，所有这些都是细胞凋亡的关键标志物（****p<0.0001，***p<0.001，**p<0.01，*p<0.05）。此外，用 4-甲基噻唑处理明显降低了 CD45 和 CD123 表面标志物，表明白血病细胞的显著表型改变（****p<0.0001）。用 4-甲基噻唑进行高剂量处理可显著增加 ROS 水平，表明氧化应激增加和细胞内自由基的存在，这有助于其细胞毒性作用（*p<0.05）。治疗后观察到 TNF-α 水平显著升高，表明存在促炎反应，可能进一步抑制白血病细胞的活力。虽然 IL-6 水平保持不变，但观察到 IL-10 水平呈剂量依赖性下降，表明肿瘤微环境中的免疫抑制条件减少（*p<0.05）。
总的来说，4-甲基噻唑通过多种细胞凋亡机制靶向白血病细胞，并改变肿瘤微环境的免疫景观，增强其治疗潜力。本研究强调了进一步临床研究的必要性，以充分利用噻唑衍生物在白血病治疗中的潜力。
