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.

中文翻译：

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褪黑素增强 ABT-737 对急性单核细胞白血病 THP-1 细胞的作用

摘要

褪黑激素（N-乙酰基-5-甲氧基色胺，MEL）是一种由松果体合成的激素。由于其抑瘤作用，可将其视为抗肿瘤剂并用于联合治疗。ABT-737 是一种 Bcl-2 抑制剂，在用诱导促凋亡信号的药物处理后可促进细胞死亡。在本研究中，研究了MEL和ABT-737对增殖和有丝分裂活性、线粒体膜电位、细胞内活性氧(ROS)产生和胞质Ca ^{2+变化的联合影响。}此外，还研究了抗凋亡蛋白和促凋亡蛋白（Bcl-2和Bax）、自噬标记物（LC3A/B（I，II））、内质网应激标记物（伴侣BIP和PDI、CHOP）的表达变化。这些条件。^{MEL 与 ABT-737 一起作用导致胞质 Ca 2+}水平增加、细胞内 ROS 产生和线粒体膜电位降低。Bcl-2含量升高，Bax含量降低。CHOP 的激活刺激自噬并导致分子伴侣 BIP 和 PDI 的合成减少。据推测，褪黑激素可以增强其他化疗药物的效果，并可用于肿瘤的治疗。