Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
Department of Biochemistry, Faculty of Pharmacy, Istanbul Yeni Yuzyil University, Istanbul, Turkey.
Arch Med Res. 2021 Apr;52(3):270-276. doi: 10.1016/j.arcmed.2020.10.022. Epub 2020 Nov 14.
Although several treatment regimens for T-cell acute lymphoblastic leukemia (T-ALL), trouble is still ongoing that relapse of disease after therapies in both pediatric and adult patients. Hence, the demand for new alternative therapeutics that are antiproliferative for cancer cells but do not harm healthy cells in treatments is increasing day by day. This study aimed to investigate whether succinic acid show anti-proliferative and apoptotic effect of on T-ALL cell lines.
Time and dose-dependent effects of succinic acid on T-ALL cell lines were determined by using WST-1, caspase-3/ bicinchoninic acid (BCA), and Annexin V-Fluorescein isothiocyanate (FITC) assays. We included the MRC-5 cell line in our study as a healthy control group.
Based on our findings, 25 and 50 mmol dosages of succinic acid has shown an apoptotic effect on T-ALL cell lines for 48 h treatment. Also, it has shown that after 48 h exposure of 25 and 50 mmol dosages of succinic acid has no significant cytotoxic effect in healthy MRC-5 cells. Apoptotic activity of succinic acid on CCRF-CEM cell line was caspase-3 dependent but not for MOLT-4. As a consequence, succinic acid was found to effect for T-ALL treatment in vitro and might also enlighten new study fields for different cancer experiments.
尽管已经有几种治疗 T 细胞急性淋巴细胞白血病(T-ALL)的方案,但儿科和成人患者在治疗后疾病仍会复发,这仍然是一个难题。因此,人们对新的治疗方法的需求日益增加,这些方法不仅对癌细胞具有抗增殖作用,而且在治疗过程中不会伤害健康细胞。本研究旨在探讨琥珀酸对 T-ALL 细胞系是否具有抗增殖和促凋亡作用。
通过 WST-1、半胱天冬酶-3/双缩脲(BCA)和 Annexin V-异硫氰酸荧光素(FITC)检测,确定琥珀酸对 T-ALL 细胞系的时间和剂量依赖性作用。我们将 MRC-5 细胞系纳入本研究作为健康对照组。
根据我们的发现,25 和 50mmol 剂量的琥珀酸在 48 小时的治疗中显示出对 T-ALL 细胞系的促凋亡作用。此外,研究表明,在 48 小时暴露于 25 和 50mmol 剂量的琥珀酸后,对健康的 MRC-5 细胞没有明显的细胞毒性作用。琥珀酸对 CCRF-CEM 细胞系的促凋亡活性依赖于半胱天冬酶-3,但对 MOLT-4 则不是。因此,琥珀酸被发现对 T-ALL 的体外治疗有效,也可能为不同的癌症实验开辟新的研究领域。