Cardiovascular Research Institute, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
Department of Neurosurgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
Cancer Sci. 2018 Nov;109(11):3483-3493. doi: 10.1111/cas.13781. Epub 2018 Oct 6.
We previously reported the efficacy of anti-cancer therapy with hyperthermia using an alternating magnetic field (AMF) and a magnetic compound. In the course of the study, unexpectedly, we found that an AMF enhances the cytotoxicity of Compound C, an activated protein kinase (AMPK) inhibitor, although this compound is not magnetic. Therefore, we examined the cellular mechanism of AMF-induced cytotoxicity of Compound C in cultured human glioblastoma (GB) cells. An AMF (280 kHz, 250 Arms) for 30 minutes significantly enhanced the cytotoxicity of Compound C and promoted apoptosis towards several human GB cell lines in vitro. The AMF also increased Compound C-induced cell-cycle arrest of GB cells at the G2 phase and, thus, inhibited cell proliferation. The AMF increased Compound C-induced reactive oxygen species production. Furthermore, the AMF decreased ERK phosphorylation in the presence of Compound C and suppressed the protective autophagy induced by this compound. The application of an AMF in cancer chemotherapy may be a simple and promising method, which might reduce the doses of drugs used in future cancer treatment and, therefore, the associated side effects.
我们之前报道了使用交变磁场 (AMF) 和磁性化合物进行的癌症热疗的疗效。在研究过程中,出乎意料的是,我们发现 AMF 增强了化合物 C(一种激活蛋白激酶 (AMPK) 抑制剂)的细胞毒性,尽管该化合物本身不具有磁性。因此,我们研究了 AMF 诱导的体外培养的人胶质母细胞瘤 (GB) 细胞中化合物 C 细胞毒性的细胞机制。280 kHz、250 Arms 的 AMF 处理 30 分钟显著增强了化合物 C 的细胞毒性,并促进了几种人 GB 细胞系的凋亡。AMF 还增加了化合物 C 诱导的 GB 细胞在 G2 期的细胞周期停滞,从而抑制了细胞增殖。AMF 增加了化合物 C 诱导的活性氧物质的产生。此外,AMF 降低了化合物 C 存在时 ERK 的磷酸化,并抑制了该化合物诱导的保护性自噬。在癌症化疗中应用 AMF 可能是一种简单而有前途的方法,它可能会减少未来癌症治疗中使用的药物剂量,从而降低相关的副作用。