Melatonin Enhances the Effect of ABT-737 in Acute Monocytic Leukemia THP-1 Cells

IF 1.5 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Biology Pub Date : 2024-02-01 DOI:10.1134/s002689332401014x

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Abstract

Melatonin (N-acetyl-5-methoxytryptamine, MEL) is a hormone synthesized by the pineal gland. Due to its oncostatic effect, it can be considered as an antitumor agent and used for combination therapy. ABT-737, a Bcl-2 inhibitor, promotes cell death after treatment with agents that induce pro-apoptotic signals. In the present study, the combined effect of MEL and ABT-737 on changes in proliferative and mitotic activity, mitochondrial membrane potential, intracellular production of reactive oxygen species (ROS), and cytosolic Ca²⁺ was studied. Moreover, changes in the expression of anti- and pro-apoptotic proteins (Bcl-2 and Bax), autophagy markers (LC3A/B (I, II)), endoplasmic reticulum stress markers (chaperones BIP and PDI, CHOP) were studied under these conditions. The effect of MEL together with ABT-737 led to an increase in the level of cytosolic Ca²⁺, intracellular production of ROS and a decrease in the membrane potential of mitochondria. The content of Bcl-2 increased, while the level of Bax decreased. Activation of CHOP stimulated autophagy and led to a decrease in the synthesis of chaperones BIP and PDI. It is assumed that melatonin can enhance the effect of other chemotherapeutic agents and can be used in the treatment of tumors.

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褪黑激素能增强 ABT-737 对急性单核细胞白血病 THP-1 细胞的作用

摘要褪黑素（N-乙酰-5-甲氧基色胺，MEL）是一种由松果体合成的激素。由于其抗癌作用，它可被视为一种抗肿瘤药物并用于联合治疗。ABT-737 是一种 Bcl-2 抑制剂，在使用诱导细胞凋亡信号的药物治疗后可促进细胞死亡。本研究研究了 MEL 和 ABT-737 对细胞增殖和有丝分裂活性、线粒体膜电位、细胞内活性氧（ROS）生成和细胞膜 Ca2+ 变化的联合影响。此外，还研究了在这些条件下抗凋亡蛋白（Bcl-2 和 Bax）、促凋亡蛋白（Bcl-2 和 Bax）、自噬标记物（LC3A/B (I, II)）、内质网应激标记物（伴侣蛋白 BIP 和 PDI、CHOP）的表达变化。MEL 和 ABT-737 的作用导致细胞膜 Ca2+ 水平升高、细胞内产生 ROS 和线粒体膜电位降低。Bcl-2 的含量增加，而 Bax 的含量下降。CHOP 的激活刺激了自噬，并导致伴侣 BIP 和 PDI 的合成减少。据推测，褪黑素能增强其他化疗药物的效果，可用于治疗肿瘤。

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来源期刊

Molecular Biology 生物-生化与分子生物学

CiteScore

1.30

自引率

8.30%

发文量

审稿时长

3 months

期刊介绍： Molecular Biology is an international peer reviewed journal that covers a wide scope of problems in molecular, cell and computational biology including genomics, proteomics, bioinformatics, molecular virology and immunology, molecular development biology, molecular evolution and related areals. Molecular Biology publishes reviews, experimental and theoretical works. Every year, the journal publishes special issues devoted to most rapidly developing branches of physical-chemical biology and to the most outstanding scientists.