4.5 Article

Alternating magnetic field enhances cytotoxicity of Compound C

Journal

CANCER SCIENCE
Volume 109, Issue 11, Pages 3483-3493

Publisher

WILEY
DOI: 10.1111/cas.13781

Keywords

alternating magnetic field; compound C; cytotoxicity; glioblastoma; proliferation

Categories

Funding

  1. Japan Society for the Promotion of Science (JSPS) KAKENHI [24390200, 25670131]
  2. Japan Agency for Medical Research and Development (AMED) [66890005, 66890011, 66890001, 66890023]
  3. Ministry of Education, Culture, Sports, Science and Technology (MEXT) KAKENHI [22136009]
  4. National Cerebral and Cardiovascular Center (NCVC) [22-2-3]
  5. New Energy and Industrial Technology Development Organization [60890021]

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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.

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