Institute of Theoretical and Experimental Biophysics, Russian Academy of Science, Institutskaya St, 3, 142290 Pushchino, Moscow region, Russia.
Pushchino State Natural Science Institute, 142290 Pushchino, Moscow region, Russia.
Int J Mol Sci. 2018 Sep 21;19(10):2873. doi: 10.3390/ijms19102873.
Melatonin is produced by the pineal gland. It can be regarded as an anticancer agent and used for combined therapy, owing to its oncostatic, antioxidant, and immunoregulatory activities. Retinoic acid is widely used for the treatment of acute promyelocytic leukemia; however, it has adverse effects on the human organism. We investigated the effect of melatonin and reduced concentrations of retinoic acid on the activation of proliferation in acute promyelocytic leukemiaon a cell model HL-60. The combined effect of these compounds leads to a reduction in the number of cells by 70% and the index of mitotic activity by 64%. Combined treatment with melatonin and retinoic acid decreased the expression of the Bcl-2. The mitochondrial isoform VDAC1 can be a target in the treatment of different tumors. The combined effect of and retinoic acid at a low concentration (10 nM) decreased VDAC1 expression. Melatonin in combination with retinoic acid produced a similar effect on the expression of the translocator protein. The coprecipitation of VDAC with 2',3'-cyclonucleotide-3'-phosphodiesterase implies a possible role of its in cancer development. The combined effect of retinoic acid and melatonin decreased the activity of the electron transport chain complexes. The changes in the activation of proliferation in HL-60 cells, the mitotic index, and Bcl-2 expression under combined effect of retinoic acid (10 nM) with melatonin (1 mM) are similar to changes that are induced by 1 μM retinoic acid. Our results suggest that MEL is able to improve the action the other chemotherapeutic agent.
褪黑素由松果体产生。由于其生长抑制、抗氧化和免疫调节作用，可将其视为一种抗癌药物，并用于联合治疗。维甲酸广泛用于治疗急性早幼粒细胞白血病，但对人体有不良影响。我们研究了褪黑素和降低浓度的维甲酸对 HL-60 细胞模型中急性早幼粒细胞白血病增殖激活的影响。这些化合物的联合作用导致细胞数量减少 70%，有丝分裂活性指数减少 64%。褪黑素和维甲酸联合治疗降低了 Bcl-2 的表达。线粒体同工型 VDAC1 可以成为治疗不同肿瘤的靶点。在低浓度（10 nM）下，维甲酸和褪黑素的联合作用降低了 VDAC1 的表达。褪黑素与维甲酸联合使用对转位蛋白的表达也产生了类似的影响。VDAC 与 2'，3'-环核苷酸-3'-磷酸二酯酶的共沉淀表明其在癌症发展中可能具有作用。维甲酸和褪黑素的联合作用降低了电子传递链复合物的活性。HL-60 细胞增殖激活、有丝分裂指数和 Bcl-2 表达的变化，在 10 nM 维甲酸与 1 mM 褪黑素的联合作用下，与 1 μM 维甲酸诱导的变化相似。我们的结果表明，MEL 能够增强其他化疗药物的作用。
