The Effect of a New Glucose-Methotrexate Conjugate on Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma Cell Lines.
Marta WozniakSebastian MakuchGabriela Pastuch-GawołekJerzy WiśniewskiWiesław SzejaMartyna NowakMonika KrawczykSiddarth AgrawalPublished in: Molecules (Basel, Switzerland) (2021)
Patients with hematologic malignancies require intensive therapies, including high-dose chemotherapy. Antimetabolite-methotrexate (MTX) has been used for many years in the treatment of leukemia and in lymphoma patients. However, the lack of MTX specificity causes a significant risk of morbidity, mortality, and severe side effects that impairs the quality of patients' life. Therefore, novel targeted therapies based on the malignant cells' common traits have become an essential treatment strategy. Glucose transporters have been found to be overexpressed in neoplastic cells, including hematologic malignancies. In this study, we biologically evaluated a novel glucose-methotrexate conjugate (Glu-MTX) in comparison to a free MTX. The research aimed to assess the effectiveness of Glu-MTX on chosen human lymphoma and leukemia cell lines. Cell cytotoxicity was verified by MTT viability test and flow cytometry. Moreover, the cell cycle and cellular uptake of Glu-MTX were evaluated. Our study reveals that conjugation of methotrexate with glucose significantly increases drug uptake and results in similar cytotoxicity of the synthesized compound. Although the finding has been confined to in vitro studies, our observations shed light on a potential therapeutic approach that increases the selectivity of chemotherapeutics and can improve leukemia and lymphoma patients' outcomes.
Keyphrases
- high dose
- end stage renal disease
- acute lymphoblastic leukemia
- ejection fraction
- cell cycle
- newly diagnosed
- chronic kidney disease
- prognostic factors
- randomized controlled trial
- acute myeloid leukemia
- diffuse large b cell lymphoma
- induced apoptosis
- peritoneal dialysis
- blood glucose
- squamous cell carcinoma
- endothelial cells
- bone marrow
- oxidative stress
- stem cells
- low dose
- flow cytometry
- emergency department
- patient reported outcomes
- adipose tissue
- signaling pathway
- dna methylation
- locally advanced
- cardiovascular disease
- blood pressure
- weight loss
- metabolic syndrome
- allogeneic hematopoietic stem cell transplantation
- endoplasmic reticulum stress
- combination therapy
- induced pluripotent stem cells
- pi k akt