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, Ying-Jan 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
Publication statusPublished - 2014 Jan 1
Event5th International Congress on Arsenic in the Environment, As 2014 - Buenos Aires, Argentina
Duration: 2014 May 112014 May 16

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
CountryArgentina
CityBuenos Aires
Period14-05-1114-05-16

Fingerprint

Cell death
Proteasome Endopeptidase Complex
Ubiquitin
Arsenic
Apoptosis
Phosphorylation
AMP-Activated Protein Kinases
Proteasome Inhibitors
Caspase 3
Tumors
arsenic trioxide
Proteins

All Science Journal Classification (ASJC) codes

  • Chemical Health and Safety

Cite this

Chiu, H. W., Tseng, Y. C., & Wang, Y-J. (2014). Arsenic trioxide induces both apoptosis and autophagy through stimulation of ER stress and inhibition of ubiquitin-proteasome system in human sarcoma cells. In One Century of the Discovery of Arsenicosis in Latin America (1914-2014): As 2014 - Proceedings of the 5th International Congress on Arsenic in the Environment (pp. 504-505). (One Century of the Discovery of Arsenicosis in Latin America (1914-2014): As 2014 - Proceedings of the 5th International Congress on Arsenic in the Environment). CRC Press/Balkema.
Chiu, H. W. ; Tseng, Y. C. ; Wang, Ying-Jan. / Arsenic trioxide induces both apoptosis and autophagy through stimulation of ER stress and inhibition of ubiquitin-proteasome system in human sarcoma cells. One Century of the Discovery of Arsenicosis in Latin America (1914-2014): As 2014 - Proceedings of the 5th International Congress on Arsenic in the Environment. CRC Press/Balkema, 2014. pp. 504-505 (One Century of the Discovery of Arsenicosis in Latin America (1914-2014): As 2014 - Proceedings of the 5th International Congress on Arsenic in the Environment).
@inproceedings{370476c044084b16b0872e9f3b04f89f,
title = "Arsenic trioxide induces both apoptosis and autophagy through stimulation of ER stress and inhibition of ubiquitin-proteasome system in human sarcoma cells",
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.",
author = "Chiu, {H. W.} and Tseng, {Y. C.} and Ying-Jan Wang",
year = "2014",
month = "1",
day = "1",
language = "English",
isbn = "9781138001411",
series = "One Century of the Discovery of Arsenicosis in Latin America (1914-2014): As 2014 - Proceedings of the 5th International Congress on Arsenic in the Environment",
publisher = "CRC Press/Balkema",
pages = "504--505",
booktitle = "One Century of the Discovery of Arsenicosis in Latin America (1914-2014)",

}

Chiu, HW, Tseng, YC & Wang, Y-J 2014, Arsenic trioxide induces both apoptosis and autophagy through stimulation of ER stress and inhibition of ubiquitin-proteasome system in human sarcoma cells. in One Century of the Discovery of Arsenicosis in Latin America (1914-2014): As 2014 - Proceedings of the 5th International Congress on Arsenic in the Environment. One Century of the Discovery of Arsenicosis in Latin America (1914-2014): As 2014 - Proceedings of the 5th International Congress on Arsenic in the Environment, CRC Press/Balkema, pp. 504-505, 5th International Congress on Arsenic in the Environment, As 2014, Buenos Aires, Argentina, 14-05-11.

Arsenic trioxide induces both apoptosis and autophagy through stimulation of ER stress and inhibition of ubiquitin-proteasome system in human sarcoma cells. / Chiu, H. W.; Tseng, Y. C.; Wang, Ying-Jan.

One Century of the Discovery of Arsenicosis in Latin America (1914-2014): As 2014 - Proceedings of the 5th International Congress on Arsenic in the Environment. CRC Press/Balkema, 2014. p. 504-505 (One Century of the Discovery of Arsenicosis in Latin America (1914-2014): As 2014 - Proceedings of the 5th International Congress on Arsenic in the Environment).

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

TY - GEN

T1 - Arsenic trioxide induces both apoptosis and autophagy through stimulation of ER stress and inhibition of ubiquitin-proteasome system in human sarcoma cells

AU - Chiu, H. W.

AU - Tseng, Y. C.

AU - Wang, Ying-Jan

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84907319351&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907319351&partnerID=8YFLogxK

M3 - Conference contribution

AN - SCOPUS:84907319351

SN - 9781138001411

T3 - One Century of the Discovery of Arsenicosis in Latin America (1914-2014): As 2014 - Proceedings of the 5th International Congress on Arsenic in the Environment

SP - 504

EP - 505

BT - One Century of the Discovery of Arsenicosis in Latin America (1914-2014)

PB - CRC Press/Balkema

ER -

Chiu HW, Tseng YC, Wang Y-J. Arsenic trioxide induces both apoptosis and autophagy through stimulation of ER stress and inhibition of ubiquitin-proteasome system in human sarcoma cells. In One Century of the Discovery of Arsenicosis in Latin America (1914-2014): As 2014 - Proceedings of the 5th International Congress on Arsenic in the Environment. CRC Press/Balkema. 2014. p. 504-505. (One Century of the Discovery of Arsenicosis in Latin America (1914-2014): As 2014 - Proceedings of the 5th International Congress on Arsenic in the Environment).