TEOA Inhibits Proliferation and Induces DNA Damage of Diffuse Large B-Cell Lymphoma Cells Through Activation of the ROS-Dependent p38 MAPK Signaling Pathway
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma, accounting for approximately 30% to 40% of non-Hodgkin’s lymphomas (NHL). The administration of rituximab significantly improved the outcomes of DLBCL; however, the unavoidable development of resistance limits the long-ter...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.554736/full |
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doaj-4a2514e9798b40ce91a07c8fb14b44e9 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Xingxing Yu Xingxing Yu Xin Wang Xu Wang Xu Wang Yi Zhou Yi Zhou Yanchun Li Aiwei Wang Tongtong Wang Yihan An Weidong Sun Jing Du Xiangmin Tong Xiangmin Tong Xiangmin Tong Xiangmin Tong Ying Wang |
| spellingShingle |
Xingxing Yu Xingxing Yu Xin Wang Xu Wang Xu Wang Yi Zhou Yi Zhou Yanchun Li Aiwei Wang Tongtong Wang Yihan An Weidong Sun Jing Du Xiangmin Tong Xiangmin Tong Xiangmin Tong Xiangmin Tong Ying Wang TEOA Inhibits Proliferation and Induces DNA Damage of Diffuse Large B-Cell Lymphoma Cells Through Activation of the ROS-Dependent p38 MAPK Signaling Pathway Frontiers in Pharmacology TEOA diffuse large B-cell lymphoma DNA damage reactive oxygen species p38 MAPK |
| author_facet |
Xingxing Yu Xingxing Yu Xin Wang Xu Wang Xu Wang Yi Zhou Yi Zhou Yanchun Li Aiwei Wang Tongtong Wang Yihan An Weidong Sun Jing Du Xiangmin Tong Xiangmin Tong Xiangmin Tong Xiangmin Tong Ying Wang |
| author_sort |
Xingxing Yu |
| title |
TEOA Inhibits Proliferation and Induces DNA Damage of Diffuse Large B-Cell Lymphoma Cells Through Activation of the ROS-Dependent p38 MAPK Signaling Pathway |
| title_short |
TEOA Inhibits Proliferation and Induces DNA Damage of Diffuse Large B-Cell Lymphoma Cells Through Activation of the ROS-Dependent p38 MAPK Signaling Pathway |
| title_full |
TEOA Inhibits Proliferation and Induces DNA Damage of Diffuse Large B-Cell Lymphoma Cells Through Activation of the ROS-Dependent p38 MAPK Signaling Pathway |
| title_fullStr |
TEOA Inhibits Proliferation and Induces DNA Damage of Diffuse Large B-Cell Lymphoma Cells Through Activation of the ROS-Dependent p38 MAPK Signaling Pathway |
| title_full_unstemmed |
TEOA Inhibits Proliferation and Induces DNA Damage of Diffuse Large B-Cell Lymphoma Cells Through Activation of the ROS-Dependent p38 MAPK Signaling Pathway |
| title_sort |
teoa inhibits proliferation and induces dna damage of diffuse large b-cell lymphoma cells through activation of the ros-dependent p38 mapk signaling pathway |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Pharmacology |
| issn |
1663-9812 |
| publishDate |
2020-09-01 |
| description |
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma, accounting for approximately 30% to 40% of non-Hodgkin’s lymphomas (NHL). The administration of rituximab significantly improved the outcomes of DLBCL; however, the unavoidable development of resistance limits the long-term efficacy. Therefore, a new generation of less toxic drugs with higher chemotherapy response is required to prevent or reverse chemoresistance. TEOA is a pentacyclic triterpenoid compound isolated from the roots of Actinidia eriantha. Studies have confirmed that TEOA has significant cytotoxicity on gastrointestinal cancer cells. However, there are no relevant reports on DLBCL cells. In this study, we investigated the potential molecular mechanism of the anticancer activity of TEOA in DLBCL cells. The results demonstrated that TEOA inhibited proliferation and induced apoptosis in time-and dose-dependent manners. TEOA induced reactive oxygen species (ROS) generation, which was reversed by N-acetyl cysteine (NAC). TEOA induced DNA damage, increased the level of γ-H2AX, and the phosphorylation of CHK1 and CHK2. In addition, TEOA induced the activation of the p38 MAPK pathway and pretreated with p38 inhibitor SB20358 or ROS scavenger could block TEOA-induced DNA damage. Taken together, these results suggest that ROS mediated activation of the p38 MAPK signal pathway plays an important role in initiating TEOA-induced DNA damage. |
| topic |
TEOA diffuse large B-cell lymphoma DNA damage reactive oxygen species p38 MAPK |
| url |
https://www.frontiersin.org/article/10.3389/fphar.2020.554736/full |
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doaj-4a2514e9798b40ce91a07c8fb14b44e92020-11-25T03:20:45ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-09-011110.3389/fphar.2020.554736554736TEOA Inhibits Proliferation and Induces DNA Damage of Diffuse Large B-Cell Lymphoma Cells Through Activation of the ROS-Dependent p38 MAPK Signaling PathwayXingxing Yu0Xingxing Yu1Xin Wang2Xu Wang3Xu Wang4Yi Zhou5Yi Zhou6Yanchun Li7Aiwei Wang8Tongtong Wang9Yihan An10Weidong Sun11Jing Du12Xiangmin Tong13Xiangmin Tong14Xiangmin Tong15Xiangmin Tong16Ying Wang17Clinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaDepartment of Hematology, Fuyang Hospital of Anhui Medical University, Fuyang, ChinaClinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaSchool of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, ChinaDepartment of Laboratory Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaClinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaWangjiangshan Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaThe Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaDepartment of Hematology, The First People’s Hospital of Fuyang, Hangzhou, ChinaWangjiangshan Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaClinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaClinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaDepartment of Laboratory Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaClinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaSchool of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, ChinaThe Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaPhase I Clinical Research Center, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaPhase I Clinical Research Center, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaDiffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma, accounting for approximately 30% to 40% of non-Hodgkin’s lymphomas (NHL). The administration of rituximab significantly improved the outcomes of DLBCL; however, the unavoidable development of resistance limits the long-term efficacy. Therefore, a new generation of less toxic drugs with higher chemotherapy response is required to prevent or reverse chemoresistance. TEOA is a pentacyclic triterpenoid compound isolated from the roots of Actinidia eriantha. Studies have confirmed that TEOA has significant cytotoxicity on gastrointestinal cancer cells. However, there are no relevant reports on DLBCL cells. In this study, we investigated the potential molecular mechanism of the anticancer activity of TEOA in DLBCL cells. The results demonstrated that TEOA inhibited proliferation and induced apoptosis in time-and dose-dependent manners. TEOA induced reactive oxygen species (ROS) generation, which was reversed by N-acetyl cysteine (NAC). TEOA induced DNA damage, increased the level of γ-H2AX, and the phosphorylation of CHK1 and CHK2. In addition, TEOA induced the activation of the p38 MAPK pathway and pretreated with p38 inhibitor SB20358 or ROS scavenger could block TEOA-induced DNA damage. Taken together, these results suggest that ROS mediated activation of the p38 MAPK signal pathway plays an important role in initiating TEOA-induced DNA damage.https://www.frontiersin.org/article/10.3389/fphar.2020.554736/fullTEOAdiffuse large B-cell lymphomaDNA damagereactive oxygen speciesp38 MAPK |