Unveiling the synergistic potential: Palm vitamin E and cytarabine combination therapy in acute myeloid leukaemia cell models

Acute myeloid leukemia (AML) represents a malignant condition of the bone marrow wherein hematopoietic precursors undergo arrest in an early developmental stage. The primary approach for treating most AML types involves chemotherapy, alongside targeted therapy drugs and stem cell transplants. In our investigation, we utilized individual isomers of palm tocotrienol and a mixed fraction known as tocotrienol-rich fraction (TRF) in combination therapy with the leukemic drug cytarabine, aiming to achieve a synergistic therapeutic effect in AML treatment. We evaluated cell viability in single and combination treatment groups using the water-soluble tetrazolium (WST) assay. Results indicated that TRF significantly inhibited cell growth in THP 1, HL 60, and Kasumi 6 cells at varying percentages (p<0.05), with the most pronounced inhibition observed in Kasumi 6 cells followed by HL 60 and THP 1 cells. In the combination study, the most significant inhibition was again observed in Kasumi 6 cells with combination treatment (p<0.05). Furthermore, we assessed the activity of caspase 3, caspase 8, and caspase 9 using a commercial kit, revealing a significant increase in all caspase activities in Kasumi 6, THP 1, and HL 60 cells compared to the control group after 72 hours of incubation. Next Generation Sequencing (NGS) analysis revealed the highest fragments per kilobase of exon per million mapped fragments (FPKM) in HL-60 cells treated with the combination of cytarabine and TRF, followed by HL-60 cells treated with cytarabine alone, suggesting a higher involvement of genes and interactions in the combination group. Furthermore, results from the NGS study indicated differential regulation of numerous key genes essential for cell viability, including oncogenes and tumor suppressor genes.