THERAPEUTICS APPROACH IN SILICO USING A COELOMIC FLUID OF LUMBRICUS RUBELLUS AS COMBINED MAPLC3-TARGETED CHEMOTHERAPY IN ACUTE MYELOID LEUKEMIA

Abstract

Leukemia ranked 11th in the incidence rate of all cancers worldwide, and acute myeloid leukemia (AML) has the highest leukemia mortality rate at 62%. Protein inhibition in the autophagy mechanism combined with cytarabine as the main chemotherapy treatment for AML can improve the effectiveness of drugs that have already developed resistance. Proteins in coelomic fluid (CFL) of Lumbricus rubellus, such as lumbrokinase, lysenin, and coelomic cytolytic factor-1 (CCF-1) are known to have potential in the treatment of cancer. The purpose of this study is to determine the potential of these proteins as candidates for co-chemotherapy agents through inhibiting microtubule-associated protein light chain 3 (MAPLC3), a protein target in the autophagy mechanism of AML, using a bioinformatics approach. To the best of our knowledge, this study was the first to explore these potential therapeutic proteins as co-chemotherapy agents for AML as well as their proposed molecular mechanisms. Their effectiveness can be predicted through in silico studies, specifically with a molecular docking method between the proteins and MAPLC3 as the target. The results show that hydrogen, hydrophobic, and electrostatics bonds are formed in lumbrokinase, lysenin, and CCF-1, and the combination of them with MAPLC3. There are several active sites on MAPLC3 that bind to lumbrokinase, lysenin, CCF-1 and the combination of them. The combination of cytarabine and CFL of Lumbricus rubellus inhibited the survival of HL-60 cells. This study revealed that lumbrokinase, lysenin, CCF-1 and the combination of them have the potential to partially inhibit MAPLC3, which then may inhibit the autophagy process.