Combination treatment with arsenic trioxide and irradiation enhances autophagic effects in U118-MG cells through increased mitotic arrest and regulation of PI3K/Akt and ERK1/2 signaling pathways

Hui Wen Chiu, Sheng Yow Ho, How Ran Guo, Ying Jan Wang

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Malignant gliomas are resistant to many kinds of treatments including chemotherapy, radiotherapy and other adjuvant therapies. Autophagy is a novel response of cancer cells to ionizing radiation (IR) or chemotherapy, but its significance and underlying mechanism remains largely elusive. Induction of autophagy in glioma cells using irradiation and arsenic trioxide (ATO) has been reported separately. However, the combined effects of ATO and IR on the cell death processes of malignant glioma cells have not been thoroughly studied, especially in U118-MG cells. In the present study, we investigated the anticancer effect of IR combined with ATO and the underlying mechanisms on U118-MG human malignant glioma cells in vitro. We found that the enhanced cytotoxic effect of IR combined with ATO was through induction of more autophagy in U118-MG cells, which were characterized by the presence of acidic vascular organelle formation, determined by electron microscopic observation and immunoblotting of LC3. Combined treatment could induce more mitotic arrest compared to ATO or IR alone. In addition, we also found that the combined treatment-induced autophagy occurred through inhibition of PI3K/Akt and activation of ERK1/2 signaling pathways. These findings suggest a potential therapeutic strategy for malignant gliomas, which are resistant to various proapoptotic therapies.

Original languageEnglish
Pages (from-to)472-483
Number of pages12
JournalAutophagy
Volume5
Issue number4
DOIs
Publication statusPublished - May 16 2009
Externally publishedYes

Keywords

  • Arsenic trioxide
  • Autophagy
  • Malignant gliomas
  • Mitotic arrest
  • Radiation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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