Thiosemicarbazone Complexes and 6-MP Suppress Acute Lymphoblastic Leukemia via the NOTCH Signaling Pathway and Regulation of LUNAR1 and NALT1 lncRNA.

Background: Acute Lymphoblastic Leukemia (ALL) is the most common type of leukemia among children. There are several types of drugs that are common in treating and controlling leukemia, including 6-M. Moreover, the anti-cancer effects of the Thiosemicarbazone-Ni complex were surveyed as well as 6-MP. The current study aimed to evaluate the effect of the Thiosemicarbazone-Ni complex in comparison with 6-MP on the expression of NALT1 and LUNAR1 LncRNAs and their target gene, NOTCH1, in the Jurkat E6.1 cell line.

Materials And Methods: Jurkat E6.1 cell was treated with 6-MP with the concentrations of 1, 5, 10, and 25μM and 0.5, 1, 2, and 5μM of Ni-nanoparticles, loaded with Thiosemicarbazone complexes for 24, 48, and 72 h.  Subsequently, the RNA extraction and cDNA synthesis were performed and the expression of NALT1, LUNAR1, NOTCH1, and GAPDH genes was surveyed by Real-time PCR. Finally, the results were analyzed by statistical analysis.

Results: The highest significant reduction in the expression of LUNAR1 was observed at 6-MP at 10μM for the first 72 h and the Thiosemicarbazone-Ni complex showed its effective dose at 5μM for 48 h. The highest decrease in NOTCH1 expression was observed in 6-MP treatment at 10μM concentration for 24h and Ni-Thiosemicarbazone treatment, the significant decrease was at 0.5μM for 72h. The most significant reduction in NALT1 expression was observed in treatment with Ni-Thiosemicarbazone complex and 6-MP at the concentrations of 2 and 10μM respectively for 24h.

Conclusion: Given the association between the aforementioned genes and the positive effects of the drugs at achieved concentrations and times, it can be concluded that Thiosemicarbazone-Ni complex and 6-MP can show putative roles in regulating the expression of studied genes.