Arsenic trioxide induces both apoptosis and autophagy through stimulation of ER stress and inhibition of ubiquitin-proteasome system in human sarcoma cells

H. W. Chiu, Y. C. Tseng, Y. J. Wang

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Osteosarcoma (HOS cells) and fibrosarcoma (HT1080 cells) were used to investigate the anti-cancer effect of arsenic trioxide (ATO) and the underlying mechanisms in vitro and in vivo. We found that ATO treatment enhanced the percentage of apoptosis and autophagy in HOS and HT1080 cells through increasing the expression of ER stress-associated protein IRE1 and led to induction of LC3-II and cleaved-caspase-3. ATO significantly decreased the phosphorylation of Akt and mTOR and increased the phosphorylation of AMPK, p38, and JNK in HOS and HT1080 cells. Combined treatment of ATO and MG-132 showed synergistic effect through induction of apoptosis and autophagy in HT1080 cells. In in vivo study, the combined treatment significantly reduced the tumor volume in SCID mice that had received a subcutaneous injection of HT1080 cells. Thus, a combination of ATO and proteasome inhibitor could be a new potential therapeutic strategy for the treatment of fibrosarcoma.

Original languageEnglish
Title of host publicationOne Century of the Discovery of Arsenicosis in Latin America (1914-2014)
Subtitle of host publicationAs 2014 - Proceedings of the 5th International Congress on Arsenic in the Environment
PublisherCRC Press/Balkema
Pages504-505
Number of pages2
ISBN (Print)9781138001411
DOIs
Publication statusPublished - 2014
Externally publishedYes
Event5th International Congress on Arsenic in the Environment, As 2014 - Buenos Aires, Argentina
Duration: May 11 2014May 16 2014

Publication series

NameOne Century of the Discovery of Arsenicosis in Latin America (1914-2014): As 2014 - Proceedings of the 5th International Congress on Arsenic in the Environment

Other

Other5th International Congress on Arsenic in the Environment, As 2014
Country/TerritoryArgentina
CityBuenos Aires
Period5/11/145/16/14

ASJC Scopus subject areas

  • Chemical Health and Safety

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