Melatonin can enhance the effect of drugs used in the treatment of leukemia

Abstract

Melatonin (N-acetyl-5-methoxytryptamine, MEL), secreted by the pineal gland, plays an important role in the regulation of the different functions in human. However, there are the facts that MEL has an antitumor effect in various types of cancer. We have studied the combined effect of MEL and targeted drugs such as cytarabine (CYT) and navitoclax (ABT-737) on the development of acute myeloid leukemia in the MV4-11 cell model. The combined action of MEL with CYT or ABT-737 contributed to a decrease in the proliferative activity of leukemia cells, a drop in the membrane potential of mitochondria, and an increase in the production of reactive oxygen species and cytosolic Ca2+. We have shown that MEL, together with CYT or ABT-737, increases expression of homologous C/EBP protein and autophagy marker LC3A/B and decreases protein disulfide isomerase and immunoglobulin-binding protein levels, and consequently modulate endoplasmic stress. reticulum and initiate autophagy. The obtained data support the earlier suggestion that MEL may have potential benefits in cancer treatment and may be considered as an additive to drugs used in therapy.