Nanosecond pulsed electric fields induce apoptosis in p53-wildtype and p53-null HCT116 colon carcinoma cells
Nanosecond pulsed electric fields induce apoptosis in p53-wildtype and p53-null HCT116 colon carcinoma cells
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DOI：
10.1007/s10495-007-0083-7
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发表时间：
2007-09-01
期刊：
影响因子：
7.2
通讯作者：
Beebe, Stephen J.
中科院分区：
文献类型：
--
作者：
Hall, Emily H.;Schoenbach, Karl H.;Beebe, Stephen J.
纳秒脉冲电场（nsPEF）产生的非电离辐射是电离辐射治疗癌症的替代方案。NsPEFS是高功率、低能量（非热）脉冲，与质膜电穿孔不同，它调节细胞内结构和功能。为了确定p53在nsPEF诱导的细胞凋亡中的功能，将HCT 116 p53（+/+）和HCT 116 p53（-/-）结肠癌细胞暴露于持续时间为60 ns或300 ns的60 kV/cm的多个脉冲，并分析细胞凋亡标志物。观察到几种凋亡标志物，包括细胞皱缩和细胞色素c阳性细胞百分比增加，活性半胱天冬酶，片段化DNA和Bax，但不是Bcl-2。与Jurkat细胞中nsPEF诱导的细胞凋亡不同（Beebe等人，2003 a），在细胞色素c增加之前观察到活性半胱天冬酶，这在存在和不存在Bax的情况下发生。细胞皱缩仅发生在Bax或细胞色素c水平升高的细胞中。NsPEFs在HCT 116 p53（+/+）和HCT 116 p53（-/-）细胞中诱导凋亡的作用相同。这些结果表明，由nsPEFs产生的非电离辐射可以作为具有治疗潜力的非配体激动剂，利用HCT 116细胞中的非肿瘤依赖性机制诱导细胞凋亡，该机制在存在或不存在p-53和Bax的情况下导致半胱天冬酶活化和细胞死亡。
Non-ionizing radiation produced by nanosecond pulsed electric fields (nsPEFs) is an alternative to ionizing radiation for cancer treatment. NsPEFs are high power, low energy (non-thermal) pulses that, unlike plasma membrane electroporation, modulate intracellular structures and functions. To determine functions for p53 in nsPEF-induced apoptosis, HCT116p53(+/+) and HCT116p53(-/-) colon carcinoma cells were exposed to multiple pulses of 60 kV/cm with either 60 ns or 300 ns durations and analyzed for apoptotic markers. Several apoptosis markers were observed including cell shrinkage and increased percentages of cells positive for cytochrome c, active caspases, fragmented DNA, and Bax, but not Bcl-2. Unlike nsPEF-induced apoptosis in Jurkat cells (Beebe et al. 2003a) active caspases were observed before increases in cytochrome c, which occurred in the presence and absence of Bax. Cell shrinkage occurred only in cells with increased levels of Bax or cytochrome c. NsPEFs induced apoptosis equally in HCT116p53(+/+) and HCT116p53(-/-) cells. These results demonstrate that non-ionizing radiation produced by nsPEFs can act as a non-ligand agonist with therapeutic potential to induce apoptosis utilizing mitochondrial-independent mechanisms in HCT116 cells that lead to caspase activation and cell death in the presence or absence of p-53 and Bax.