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 |
| 卷 | 119 |
| 發行號 | 6 |
| DOIs | |
| 出版狀態 | Published - 2018 六月 |
指紋
All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
引用此文
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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, Ta Shen; Huang, Bu Miin; Wang, Chia Yih.
於: Journal of Cellular Biochemistry, 卷 119, 編號 6, 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, Ta Shen
AU - Huang, Bu Miin
AU - Wang, Chia Yih
PY - 2018/6
Y1 - 2018/6
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.
UR - http://www.scopus.com/inward/record.url?scp=85042535084&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042535084&partnerID=8YFLogxK
U2 - 10.1002/jcb.26652
DO - 10.1002/jcb.26652
M3 - Article
C2 - 29280173
AN - SCOPUS:85042535084
VL - 119
SP - 4729
EP - 4741
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
SN - 0730-2312
IS - 6
ER -