Normothermic Microwave Irradiation Induces Death of HL-60 Cells through Heat-Independent Apoptosis.

Normothermic Microwave Irradiation Induces Death of HL-60 Cells through Heat-Independent Apoptosis.
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DOI:
10.1038/s41598-017-11784-y
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发表时间:
2017-09-12
期刊:
影响因子:
4.6
通讯作者:
Tabuse K
Tabuse K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Asano M;Tanaka S;Sakaguchi M;Matsumura H;Yamaguchi T;Fujita Y;Tabuse K

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微波已用于各种癌症治疗以产生热量并增加肿瘤细胞温度;然而,它们的使用受到其在正常细胞中的副作用和获得耐热性的限制。我们之前开发了一种微波辐射方法,通过在治疗期间保持37 °C的细胞温度来杀死培养的癌细胞,包括人早幼粒单核细胞白血病(HL-60)细胞系。在本研究中,我们研究了HL-60细胞死亡的机制,在这种处理。微波照射的HL-60细胞似乎经历caspase-独立的凋亡,从而诱导线粒体功能障碍相关的凋亡诱导因子(AIF)表达的DNA片段。凋亡蛋白酶激活因子1(Apaf-1)和半胱天冬酶9的丢失也中断了半胱天冬酶依赖性凋亡。此外,这些细胞没有表现出热应激反应,如缺乏热休克蛋白70(HSP 70)上调所示。或者,在42.5 °C加热的HL-60细胞中,HSP 70表达上调,类似于死亡受体诱导的凋亡的途径被激活,同时线粒体功能得以维持。总的来说,这些结果表明,我们的37 °C微波辐射方法激活的细胞死亡途径与其他加热方法诱导的细胞死亡途径不同,并支持在临床癌症治疗中使用常温微波辐射。
Microwaves have been used in various cancer therapies to generate heat and increase tumor cell temperature; however, their use is limited by their side-effects in normal cells and the acquisition of heat resistance. We previously developed a microwave irradiation method that kills cultured cancer cells, including a human promyelomonocytic leukemia (HL-60) cell line, by maintaining a cellular temperature of 37 °C during treatment. In the present study, we investigated the mechanisms underlying HL-60 cell death during this treatment. The microwave-irradiated HL-60 cells appear to undergo caspase-independent apoptosis, whereby DNA fragmentation was induced by mitochondrial dysfunction-related expression of apoptosis-inducing factor (AIF). Caspase-dependent apoptosis was also interrupted by the loss of apoptotic protease-activating factor 1 (Apaf-1) and caspase 9. Moreover, these cells did not exhibit a heat-stress response, as shown by the lack of heat shock protein 70 (HSP70) upregulation. Alternatively, in HL-60 cells heated at 42.5 °C, HSP70 expression was upregulated and a pathway resembling death receptor-induced apoptosis was activated while mitochondrial function was maintained. Collectively, these results suggest that the cell death pathway activated by our 37 °C microwave irradiation method differs from that induced during other heating methods and support the use of normothermic microwave irradiation in clinical cancer treatments.
DOI: 10.1038/srep41244
发表时间: 2017-02-01
期刊: Scientific reports
影响因子: 4.6
作者:
Asano M;Sakaguchi M;Tanaka S;Kashimura K;Mitani T;Kawase M;Matsumura H;Yamaguchi T;Fujita Y;Tabuse K
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