DIFFERENT TYPE OF CELL DEATH INDUCTION BY CURCUMIN, ARSENIC TRIOXIDE AND DEGRASYN (WP1130) IN HUMAN MULTIPLE MYELOMA CELLS

Curcumin has been shown to inhibit the activation of nuclear factor-κB (NF-κB), which is closely linked to chemo-resistance, in multiple myeloma cells. Malignant cells of this kind typically develop progressive multidrug resistance. Our aim was to investigate new possibilities for overcoming this resistance by suppressing cell signaling pathways. MTT-dye reduction assay was used to evaluate the cytotoxic activity of degrasyn, curcumin and Arsenic (ATO) on U-266, RPMI-8226 cell lines. Carfilzomib served as reference drug. Western blot analysis was performed. In RPMI-8226 cells evident activation of caspase 3 by ATO was seen. PARP cleavage was detected after degrasyn treatment. Curcumin led to PARP degradation as well. Caspase 9 was found to be activated by ATO, degrasyn and Carfilzomib. LC3b (autophagy hallmark) level was increased after exposure to ATO, curcumin and degrasyn. In U-266 cells significant LC3b increase was recorded after carfilzomib treatment. Procaspase 9 was cleaved after curcumin usage. Degrasyn activated procaspase 3. Elisa test was performed. All substances showed inhibition of NF-κB p65 fraction in both U-266 and RPMI-8226 cell lines. Proteomic analysis was performed with Curcumin and Arsenic in U-266 cell line. Significant up regulation of pro-apoptotic proteins was seen, evident down regulation of anti-apoptotic pathways was visible as well. Taken together our data showed that all studied compounds induced different forms of cell death. Despite both cell lines RPMI-8226 and U-266 originate from patients with multiple myeloma they substantially differ in their pattern of induced cell death, which could be explained by the essential heterogenicity of this specific NHL malignancy.