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The mechanism of apoptosis in human acute promyelocytic leukemia cells treated with sorafenib and lithium chloride [Int J Med Biochem ]
Int J Med Biochem . Ahead of Print: IJMB-19484 | DOI: 10.14744/ijmb.2019.19484

The mechanism of apoptosis in human acute promyelocytic leukemia cells treated with sorafenib and lithium chloride

Aysun Ekinci1, Safiye Kaya2
1Department of Medical Biochemistry, University of Dicle, Diyarbakır, Turkey
2Department of Medical Biochemistry, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey

INTRODUCTION: In this study, we aimed to elucidate the mechanisms of sorafenib (SOR) and lithium chloride (LiCl) that cause apoptosis in acute promyleocytic leukemia (APL) HL 60 cell lineage.
METHODS: HL 60 cells were treated with 100 µM SOR and LiCl determined as the inhibition concentration value (ID50), control group was not treated. Cells were collected at the end of 24, 48 and 72 hr, cell proliferation and apoptotic index were assessed using hemocytometer and flow cytometry analysis, respectively. Cells were collected at the end of 24, 48 and 72 hr, cell proliferation and apoptotic index were assessed using hemocytometer and flow cytometry analysis, respectively. The levels of caspase-3, p-GSK-3β, p-AKT, p-ERK, p-38, p-c-jun and p-IκBα were analyzed by ELISA. The effects of drugs on cell ultrastructure were evaluated by transmission electron microscopy (TEM).
RESULTS: Single and combination drug administration decreased cell proliferation and increased apoptosis rate (p<0.01, p <0.01). The increase in apoptosis in SOR+LiCl group was higher compared to SOR group (p <0.01). However, there was no significant increase compared to LiCl. Both drugs increased caspase-3 levels (p<0.01, p<0.01), LiCl increased caspase-3 activity more than SOR. Although SOR p-GSK-3β levels (p<0.01), it was seen that LiCl increased (p> 0.05). Combined therapy decreased p-AKT, p-38 levels (p<0.01, p <0.01) whereas did not affect p-ERK, p-IκBα, p-c jun levels (p> 0.05). TEM examination showed severe lytic cytoplasmic damage and apoptotic morphology in the cells, thus increasing the rate of apoptosis was also observed microscopically.
DISCUSSION AND CONCLUSION: This study demonstrates that in human APL cells treated with both drugs, tumor cells decreased with increasing apoptotic cell numbers. It may be preferred as a new drug combination in patients with APL and mood disorder.

Keywords: Sorafenib, lithium chloride, apoptosis, acute promyleocytic leukemia, cell signaling pathway



Corresponding Author: Aysun Ekinci, Türkiye
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