7-hydroxy-staurosporine, UCN-01, induces DNA damage response, and autophagy in human osteosarcoma U2-OS cells

Wei-Chih Lien, Ting Yu Chen, Shi Yuan Sheu, Tzu Chien Lin, Fu Chi Kang, Chung Hsing Yu, Da-Shen Kuan, Bu-Miin Huang, Chia-Yih Wang

研究成果: Article

2 引文 (Scopus)

摘要

Human osteosarcoma (bone cancer) is a highly malignant and the most prevalent bone tumor affecting children. Despite recent advances in the understanding of the molecular mechanism by which anticancer drugs kill osteosarcoma or block its growth, however, the mortality rate has declined only modestly. Thus, a new therapeutic approach is needed to be established. 7-hydroxystaurosporine, UCN-01, abrogates the G2 checkpoint thus enhancing the cytotoxicity of chemotherapeutic agents. In addition, it has been evaluated in clinical trials as a single antineoplastic agent in treating several cancers. However, the effects of UCN-01 on treating bone cancer has never been tested. In this study, we found that UCN-01 induced cell cycle arrest and apoptosis in the human osteosarcoma, U2-OS cells. In addition, the migration ability was also reduced, suggesting UCN-01 inhibited cell growth and migration. When U2-OS cells were treated with UCN-01, DNA damage response was triggered. The ataxia telangiectasia mutated (ATM) and the non-canonical downstream effector, ERK, was activated by UCN-01. In addition, depletion of ATM or inhibition of ERK deteriorated the cell viability in UCN-01-treated U2-OS cells. Furthermore, UCN-01 induced autophagy activation for protecting cells from apoptosis. Thus, UCN-01 might function as a single antineoplastic agent in treating human osteosarcoma.

原文English
頁(從 - 到)4729-4741
頁數13
期刊Journal of Cellular Biochemistry
119
發行號6
DOIs
出版狀態Published - 2018 六月 1

指紋

Autophagy
Osteosarcoma
DNA Damage
DNA
Ataxia Telangiectasia
Bone Neoplasms
Bone
Antineoplastic Agents
Cells
7-hydroxystaurosporine
Apoptosis
Cell growth
Cytotoxicity
Growth
Cell Cycle Checkpoints
Cell Movement
Tumors
Neoplasms
Cell Survival
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

引用此文

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title = "7-hydroxy-staurosporine, UCN-01, induces DNA damage response, and autophagy in human osteosarcoma U2-OS cells",
abstract = "Human osteosarcoma (bone cancer) is a highly malignant and the most prevalent bone tumor affecting children. Despite recent advances in the understanding of the molecular mechanism by which anticancer drugs kill osteosarcoma or block its growth, however, the mortality rate has declined only modestly. Thus, a new therapeutic approach is needed to be established. 7-hydroxystaurosporine, UCN-01, abrogates the G2 checkpoint thus enhancing the cytotoxicity of chemotherapeutic agents. In addition, it has been evaluated in clinical trials as a single antineoplastic agent in treating several cancers. However, the effects of UCN-01 on treating bone cancer has never been tested. In this study, we found that UCN-01 induced cell cycle arrest and apoptosis in the human osteosarcoma, U2-OS cells. In addition, the migration ability was also reduced, suggesting UCN-01 inhibited cell growth and migration. When U2-OS cells were treated with UCN-01, DNA damage response was triggered. The ataxia telangiectasia mutated (ATM) and the non-canonical downstream effector, ERK, was activated by UCN-01. In addition, depletion of ATM or inhibition of ERK deteriorated the cell viability in UCN-01-treated U2-OS cells. Furthermore, UCN-01 induced autophagy activation for protecting cells from apoptosis. Thus, UCN-01 might function as a single antineoplastic agent in treating human osteosarcoma.",
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7-hydroxy-staurosporine, UCN-01, induces DNA damage response, and autophagy in human osteosarcoma U2-OS cells. / Lien, Wei-Chih; Chen, Ting Yu; Sheu, Shi Yuan; Lin, Tzu Chien; Kang, Fu Chi; Yu, Chung Hsing; Kuan, Da-Shen; Huang, Bu-Miin; Wang, Chia-Yih.

於: Journal of Cellular Biochemistry, 卷 119, 編號 6, 01.06.2018, p. 4729-4741.

研究成果: Article

TY - JOUR

T1 - 7-hydroxy-staurosporine, UCN-01, induces DNA damage response, and autophagy in human osteosarcoma U2-OS cells

AU - Lien, Wei-Chih

AU - Chen, Ting Yu

AU - Sheu, Shi Yuan

AU - Lin, Tzu Chien

AU - Kang, Fu Chi

AU - Yu, Chung Hsing

AU - Kuan, Da-Shen

AU - Huang, Bu-Miin

AU - Wang, Chia-Yih

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Human osteosarcoma (bone cancer) is a highly malignant and the most prevalent bone tumor affecting children. Despite recent advances in the understanding of the molecular mechanism by which anticancer drugs kill osteosarcoma or block its growth, however, the mortality rate has declined only modestly. Thus, a new therapeutic approach is needed to be established. 7-hydroxystaurosporine, UCN-01, abrogates the G2 checkpoint thus enhancing the cytotoxicity of chemotherapeutic agents. In addition, it has been evaluated in clinical trials as a single antineoplastic agent in treating several cancers. However, the effects of UCN-01 on treating bone cancer has never been tested. In this study, we found that UCN-01 induced cell cycle arrest and apoptosis in the human osteosarcoma, U2-OS cells. In addition, the migration ability was also reduced, suggesting UCN-01 inhibited cell growth and migration. When U2-OS cells were treated with UCN-01, DNA damage response was triggered. The ataxia telangiectasia mutated (ATM) and the non-canonical downstream effector, ERK, was activated by UCN-01. In addition, depletion of ATM or inhibition of ERK deteriorated the cell viability in UCN-01-treated U2-OS cells. Furthermore, UCN-01 induced autophagy activation for protecting cells from apoptosis. Thus, UCN-01 might function as a single antineoplastic agent in treating human osteosarcoma.

AB - Human osteosarcoma (bone cancer) is a highly malignant and the most prevalent bone tumor affecting children. Despite recent advances in the understanding of the molecular mechanism by which anticancer drugs kill osteosarcoma or block its growth, however, the mortality rate has declined only modestly. Thus, a new therapeutic approach is needed to be established. 7-hydroxystaurosporine, UCN-01, abrogates the G2 checkpoint thus enhancing the cytotoxicity of chemotherapeutic agents. In addition, it has been evaluated in clinical trials as a single antineoplastic agent in treating several cancers. However, the effects of UCN-01 on treating bone cancer has never been tested. In this study, we found that UCN-01 induced cell cycle arrest and apoptosis in the human osteosarcoma, U2-OS cells. In addition, the migration ability was also reduced, suggesting UCN-01 inhibited cell growth and migration. When U2-OS cells were treated with UCN-01, DNA damage response was triggered. The ataxia telangiectasia mutated (ATM) and the non-canonical downstream effector, ERK, was activated by UCN-01. In addition, depletion of ATM or inhibition of ERK deteriorated the cell viability in UCN-01-treated U2-OS cells. Furthermore, UCN-01 induced autophagy activation for protecting cells from apoptosis. Thus, UCN-01 might function as a single antineoplastic agent in treating human osteosarcoma.

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