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Arsenic trioxide induces autophagic cell death in osteosarcoma cells via the ROS-TFEB signaling pathway.
Biochem Biophys Res Commun. 2018 01 29; 496(1):167-175.BB

Abstract

Osteosarcoma is a common primary malignant bone tumor, the cure rate of which has stagnated over the past 25-30 years. Autophagy modulation has been considered a potential therapeutic strategy for osteosarcoma, and previous study indicated that arsenic trioxide (ATO) exhibits significant anti-carcinogenic activity. However, the ability of ATO to induce autophagy and its role in osteosarcoma cell death remains unclear. In the present study, we showed that ATO increased autophagic flux in the human osteosarcoma cell line MG-63, as evidenced by the upregulation of LC3-II and downregulation of P62/SQSTM1. Moreover, the pharmacological or genetic blocking autophagy decreased ATO -induced cell death, indicating that ATO triggered autophagic cell death in MG-63 cells. Mechanistically, ATO induced TFEB(Ser142) dephosphorylation, activated TFEB nuclear translocation and increased TFEB reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes and subsequently initiated autophagic cell death in MG-63 cells. Importantly, ATO triggered the generation of ROS in MG-63 cells. Furthermore, NAC, an ROS scavenger, abrogated the effects of ATO on TFEB-dependent autophagic cell death. Taken together, these data demonstrate that ATO induces osteosarcoma cell death via inducing excessive autophagy, which is mediated through the ROS-TFEB pathway. The present study provides a new anti-tumor mechanism of ATO treatment in osteosarcoma.

Authors+Show Affiliations

Department of Orthopedics and Trauma Surgery, Central Hospital of Zhuzhou City and Affiliated Zhuzhou Hospital of Xiangya Medical College of Central South University, Hunan, 412000, China.Surgery Department of Galactophore, Central Hospital of Zhuzhou City and Affiliated Zhuzhou Hospital of Xiangya Medical College of Central South University, Hunan, 412000, China.Department of Orthopedics Surgery, Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.Department of Orthopedics and Trauma Surgery, Central Hospital of Zhuzhou City and Affiliated Zhuzhou Hospital of Xiangya Medical College of Central South University, Hunan, 412000, China.Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China. Electronic address: hepeiheng1234@sina.com.Department of Orthopedics and Trauma Surgery, Central Hospital of Zhuzhou City and Affiliated Zhuzhou Hospital of Xiangya Medical College of Central South University, Hunan, 412000, China. Electronic address: xipingzhangsci2017@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29307831

Citation

Wu, Bowen, et al. "Arsenic Trioxide Induces Autophagic Cell Death in Osteosarcoma Cells Via the ROS-TFEB Signaling Pathway." Biochemical and Biophysical Research Communications, vol. 496, no. 1, 2018, pp. 167-175.
Wu B, Tan M, Cai W, et al. Arsenic trioxide induces autophagic cell death in osteosarcoma cells via the ROS-TFEB signaling pathway. Biochem Biophys Res Commun. 2018;496(1):167-175.
Wu, B., Tan, M., Cai, W., Wang, B., He, P., & Zhang, X. (2018). Arsenic trioxide induces autophagic cell death in osteosarcoma cells via the ROS-TFEB signaling pathway. Biochemical and Biophysical Research Communications, 496(1), 167-175. https://doi.org/10.1016/j.bbrc.2018.01.018
Wu B, et al. Arsenic Trioxide Induces Autophagic Cell Death in Osteosarcoma Cells Via the ROS-TFEB Signaling Pathway. Biochem Biophys Res Commun. 2018 01 29;496(1):167-175. PubMed PMID: 29307831.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Arsenic trioxide induces autophagic cell death in osteosarcoma cells via the ROS-TFEB signaling pathway. AU - Wu,Bowen, AU - Tan,Miduo, AU - Cai,Weiliang, AU - Wang,Biao, AU - He,Peiheng, AU - Zhang,Xiping, Y1 - 2018/01/04/ PY - 2018/01/02/received PY - 2018/01/03/accepted PY - 2018/1/9/pubmed PY - 2018/2/16/medline PY - 2018/1/9/entrez KW - Arsenic trioxide KW - Autophagy KW - Osteosarcoma KW - Reactive oxygen species KW - TFEB SP - 167 EP - 175 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 496 IS - 1 N2 - Osteosarcoma is a common primary malignant bone tumor, the cure rate of which has stagnated over the past 25-30 years. Autophagy modulation has been considered a potential therapeutic strategy for osteosarcoma, and previous study indicated that arsenic trioxide (ATO) exhibits significant anti-carcinogenic activity. However, the ability of ATO to induce autophagy and its role in osteosarcoma cell death remains unclear. In the present study, we showed that ATO increased autophagic flux in the human osteosarcoma cell line MG-63, as evidenced by the upregulation of LC3-II and downregulation of P62/SQSTM1. Moreover, the pharmacological or genetic blocking autophagy decreased ATO -induced cell death, indicating that ATO triggered autophagic cell death in MG-63 cells. Mechanistically, ATO induced TFEB(Ser142) dephosphorylation, activated TFEB nuclear translocation and increased TFEB reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes and subsequently initiated autophagic cell death in MG-63 cells. Importantly, ATO triggered the generation of ROS in MG-63 cells. Furthermore, NAC, an ROS scavenger, abrogated the effects of ATO on TFEB-dependent autophagic cell death. Taken together, these data demonstrate that ATO induces osteosarcoma cell death via inducing excessive autophagy, which is mediated through the ROS-TFEB pathway. The present study provides a new anti-tumor mechanism of ATO treatment in osteosarcoma. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/29307831/Arsenic_trioxide_induces_autophagic_cell_death_in_osteosarcoma_cells_via_the_ROS_TFEB_signaling_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(18)30018-4 DB - PRIME DP - Unbound Medicine ER -