SYNERGISTIC INDUCTION OF APOPTOSIS IN A CELL MODEL OF HUMAN LEUKEMIA K562 BY NITROGLYCERINE AND VALPROIC ACID

被引:10
作者
Aalaei, Shahin [1 ]
Mohammadzadeh, Mehdi [2 ]
Pazhang, Yaghub [2 ]
机构
[1] Urmia Univ, Fac Sci, Dept Biol, Sci Biochem, POB 165, Orumiyeh 5756151818, Iran
[2] Urmia Univ, Fac Sci, Dept Biol, POB 165, Orumiyeh 5756151818, Iran
来源
EXCLI JOURNAL | 2019年 / 18卷
关键词
Apoptosis; combination therapy; cytotoxicity; K562; cells; nitroglycerine; valproic acid; HISTONE DEACETYLASE INHIBITOR; NITRIC-OXIDE; CANCER-THERAPY; IN-VITRO; CYCLE ARREST; PROLIFERATION; COMBINATION; ACTIVATION; PROTEINS; MECHANISMS;
D O I
10.17179/excli2019-1581
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Nitroglycerin (NG), a nitric oxide donor, and valproic acid (VPA), an inhibitor of histone deacetylases, have impressive effects on numerous cancer cell lines. This study intended to evaluate synergistic effects of NG and VPA on cell viability and apoptosis in K562 cells. K562 cells were cultured in RPMI-1640 supplemented with 10 % heat-inactivated FBS. They were treated with different doses of NG, VPA and cisplatin for 24, 48, and 72 h, and MTT assay was performed to analyze cell viability. Also, Peripheral blood mononuclear cells (PBMC) were cultured in RPMI-1640 media and incubated with NG (200 mu M), VAP (100 mu M), NG+VPA (150 mu M) and cisplatin (8 mu M) to evaluate cytotoxicity. IC50 of the drugs, when they were applied separately and in combination, were calculated using the COMPUSYN software. DNA electrophoresis, TUNEL assay, and Hoechst staining were performed to investigate apoptosis induction. RT-PCR was used for the evaluation of apoptotic genes expression. The results of the MTT assay showed that cell viability decreased at all applied doses of NG and WA. It was noticed that the cytotoxic effects of these drugs were dose- and time-dependent. Based on the COMPUSYN output, the combination of the drugs (VPA and NG) in a certain ratio concentration synergistically decreased cell viability. Cisplatin significantly decreased cell viability of PBMCs and K562 cells. Also, the combination drug had cytotoxic effect and significantly reduced viability of K562 cells compared with PBMCs and control cells. In the target cells treated with this combination, Bax and caspase-3 expression increased but Bcl-2 expression decreased. These results suggest that NG, VPA, and their combination decreased cell viability and induced apoptosis via the intrinsic apoptotic pathway. This study suggests that this combination therapy can be considered for further evaluation as an effective chemotherapeutic strategy for patients with chronic myeloid leukemia.
引用
收藏
页码:619 / 630
页数:12
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