DIFFERENT TYPE OF CELL DEATH INDUCTION BY CURCUMIN, ARSENIC TRIOXIDE AND DEGRASYN (WP1130) IN HUMAN MULTIPLE MYELOMA CELLSAbstract
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.
K. Kaloyanov *, P. Donchev, M. Yotova, G. Momekov and S. Konstantinov
Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria
26 December, 2016
10 February, 2017
17 February, 2017
01 July, 2017