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- Title
CELL DEATH INDUCTION IN CANCER TREATMENT, WHAT WE SHOULD EXPECT? A STUDY ON UT7 LEUKEMIA.
- Authors
Maida, Hadžić Omanović; Lejla, Pojskić; Sanin, Haverić
- Abstract
Antitumor approaches attempt to inhibit the growth, differentiation and proliferation of cancer cells, which is a major challenge in defining appropriate therapeutic strategies. The development and efficacy of precision medicines intended to target cancerous but not healthy cells are preceded by a clear definition of the nature, mechanisms and consequences of their action, which depends on the type, sensitivity and specificity of cancer. A special approach is directed towards the discovery of antitumor mechanisms based on the cell death induction, mainly apoptosis, in different types of hematological cancers. We used a cell culture model of human acute myeloid leukemia UT-7 to analyse the apoptosis-based antitumor potential of halogenated boroxin (HB), at the cellular and molecular levels. Comparative treatments were done in peripheral blood mononuclear cells (PBMCs) obtained from tumor-healthy individuals. Methods for assessing the cell viability and cytotoxicity, apoptosis detection at the cellular level, relative expression analysis of 84 apoptosis-associated genes and expression of the antiapoptotic BCL-2 were used. The results showed high HB potential in inhibition of cell viability, induction of cytotoxicity and apoptosis with measurable dose-dependent differences in reported effects between UT-7 and PBM cells. We observed that HB affected expression of 21 genes, primarily down-regulated anti-apoptotic genes in leukemia cells. Prediction of functional association of deregulated genes inferred HB impact on NF-κB signaling pathway inhibition, mostly active in different cancers. Significant decrease of BCL-2 expression (p=0.04) was found only in UT-7 cells that confirmed their pro-survival inhibition and active apoptotic process. This study provides a strong basis for further research of the HB selective antitumor activity, with a clear effect on cell death regulation in cancers via NF-κB signaling pathway inhibition. Our results warrant further study on HB use as precision apoptosis inducers in leukemia. Even though the underlying mechanism of HB action is still unknown, the elucidation of the induction process and types of cell death may lead to applied therapeutic solutions.
- Subjects
CELL death; BCL genes; MONONUCLEAR leukocytes; CANCER cell differentiation; CELLULAR control mechanisms; CANCER treatment; ACUTE myeloid leukemia
- Publication
Genetics & Applications, 2023, p22
- ISSN
2566-2937
- Publication type
Article