Aspirin Inhibits Natural Killer/T-Cell Lymphoma by Modulation of VEGF Expression and Mitochondrial Function
Extranodal nasal-type natural killer/T-cell lymphoma (NKTCL) is an Epstein-Barr virus (EBV)-associated lymphoma with a strong tendency relapse or be refractory in response to chemotherapy. Development of a new strategy for NKTCL treatment is still quite necessary. In this study, we found that aspiri...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2018.00679/full |
| _version_ | 1818951271517782016 |
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| author | Hongyu Zhang Jianping Lu Yun Jiao Qi Chen Min Li Zichen Wang Zhendong Yu Xiaodong Huang Athena Yao Qiong Gao Weiguo Xie Ling Li Paul Yao Paul Yao Paul Yao Paul Yao |
| author_facet | Hongyu Zhang Jianping Lu Yun Jiao Qi Chen Min Li Zichen Wang Zhendong Yu Xiaodong Huang Athena Yao Qiong Gao Weiguo Xie Ling Li Paul Yao Paul Yao Paul Yao Paul Yao |
| author_sort | Hongyu Zhang |
| collection | DOAJ |
| description | Extranodal nasal-type natural killer/T-cell lymphoma (NKTCL) is an Epstein-Barr virus (EBV)-associated lymphoma with a strong tendency relapse or be refractory in response to chemotherapy. Development of a new strategy for NKTCL treatment is still quite necessary. In this study, we found that aspirin treatment suppresses VEGF expression in NKTCL SNK-6 cells. Further investigation showed that aspirin treatment increases histone methylation in the range of −100~0 that is proximal to the transcription start site on the VEGF promoter, subsequently decreasing the binding ability of Sp1 to the VEGF promoter with VEGF suppression. Furthermore, aspirin treatment modulates mitochondrial function with increased ROS formation and apoptosis in NKTCL cells. Aspirin treatment alone slightly inhibits NKTCL SNK-6 tumor growth and EBV replication; while in the presence of histone deacetylase inhibitor (HDACi) chidamide (CDM), aspirin significantly suppresses the VEGF signaling pathway with increased ROS overgeneration and EBV inhibition. We also showed that with the addition of chidamide, aspirin significantly suppresses NKTCL tumor growth in both in vitro cell culture and in vivo mouse model with prolonged mouse survival. This is the first time that the potential mechanism for aspirin-mediated VEGF suppression and anti-tumor effect has been discovered, and this study provides a new strategy for anti-tumor drug development for NKTCL treatment based on aspirin-mediated targeting of the VEGF signaling pathway and ROS formation. |
| first_indexed | 2024-12-20T09:31:50Z |
| format | Article |
| id | doaj.art-069c0320334648e18f7e15c6530f6b22 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T09:31:50Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-069c0320334648e18f7e15c6530f6b222022-12-21T19:45:05ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-01-01810.3389/fonc.2018.00679435660Aspirin Inhibits Natural Killer/T-Cell Lymphoma by Modulation of VEGF Expression and Mitochondrial FunctionHongyu Zhang0Jianping Lu1Yun Jiao2Qi Chen3Min Li4Zichen Wang5Zhendong Yu6Xiaodong Huang7Athena Yao8Qiong Gao9Weiguo Xie10Ling Li11Paul Yao12Paul Yao13Paul Yao14Paul Yao15Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, ChinaDepartment of Child Psychiatry, Kangning Hospital of Shenzhen, Shenzhen, ChinaDepartment of Pediatrics, Hainan Maternal and Child Health Hospital, Haikou, ChinaDepartment of Hematology, Peking University Shenzhen Hospital, Shenzhen, ChinaInstitute of Rehabilitation Center, Tongren Hospital of Wuhan University, Wuhan, ChinaDepartment of Child Psychiatry, Kangning Hospital of Shenzhen, Shenzhen, ChinaDepartment of Hematology, Peking University Shenzhen Hospital, Shenzhen, ChinaInstitute of Rehabilitation Center, Tongren Hospital of Wuhan University, Wuhan, ChinaInstitute of Rehabilitation Center, Tongren Hospital of Wuhan University, Wuhan, ChinaDepartment of Gynecology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaInstitute of Rehabilitation Center, Tongren Hospital of Wuhan University, Wuhan, ChinaDepartment of Pediatrics, Hainan Maternal and Child Health Hospital, Haikou, ChinaDepartment of Hematology, Peking University Shenzhen Hospital, Shenzhen, ChinaDepartment of Child Psychiatry, Kangning Hospital of Shenzhen, Shenzhen, ChinaDepartment of Pediatrics, Hainan Maternal and Child Health Hospital, Haikou, ChinaInstitute of Rehabilitation Center, Tongren Hospital of Wuhan University, Wuhan, ChinaExtranodal nasal-type natural killer/T-cell lymphoma (NKTCL) is an Epstein-Barr virus (EBV)-associated lymphoma with a strong tendency relapse or be refractory in response to chemotherapy. Development of a new strategy for NKTCL treatment is still quite necessary. In this study, we found that aspirin treatment suppresses VEGF expression in NKTCL SNK-6 cells. Further investigation showed that aspirin treatment increases histone methylation in the range of −100~0 that is proximal to the transcription start site on the VEGF promoter, subsequently decreasing the binding ability of Sp1 to the VEGF promoter with VEGF suppression. Furthermore, aspirin treatment modulates mitochondrial function with increased ROS formation and apoptosis in NKTCL cells. Aspirin treatment alone slightly inhibits NKTCL SNK-6 tumor growth and EBV replication; while in the presence of histone deacetylase inhibitor (HDACi) chidamide (CDM), aspirin significantly suppresses the VEGF signaling pathway with increased ROS overgeneration and EBV inhibition. We also showed that with the addition of chidamide, aspirin significantly suppresses NKTCL tumor growth in both in vitro cell culture and in vivo mouse model with prolonged mouse survival. This is the first time that the potential mechanism for aspirin-mediated VEGF suppression and anti-tumor effect has been discovered, and this study provides a new strategy for anti-tumor drug development for NKTCL treatment based on aspirin-mediated targeting of the VEGF signaling pathway and ROS formation.https://www.frontiersin.org/article/10.3389/fonc.2018.00679/fullaspirinepstein-barr virusmitochondriaNKTCLreactive oxygen species |
| spellingShingle | Hongyu Zhang Jianping Lu Yun Jiao Qi Chen Min Li Zichen Wang Zhendong Yu Xiaodong Huang Athena Yao Qiong Gao Weiguo Xie Ling Li Paul Yao Paul Yao Paul Yao Paul Yao Aspirin Inhibits Natural Killer/T-Cell Lymphoma by Modulation of VEGF Expression and Mitochondrial Function Frontiers in Oncology aspirin epstein-barr virus mitochondria NKTCL reactive oxygen species |
| title | Aspirin Inhibits Natural Killer/T-Cell Lymphoma by Modulation of VEGF Expression and Mitochondrial Function |
| title_full | Aspirin Inhibits Natural Killer/T-Cell Lymphoma by Modulation of VEGF Expression and Mitochondrial Function |
| title_fullStr | Aspirin Inhibits Natural Killer/T-Cell Lymphoma by Modulation of VEGF Expression and Mitochondrial Function |
| title_full_unstemmed | Aspirin Inhibits Natural Killer/T-Cell Lymphoma by Modulation of VEGF Expression and Mitochondrial Function |
| title_short | Aspirin Inhibits Natural Killer/T-Cell Lymphoma by Modulation of VEGF Expression and Mitochondrial Function |
| title_sort | aspirin inhibits natural killer t cell lymphoma by modulation of vegf expression and mitochondrial function |
| topic | aspirin epstein-barr virus mitochondria NKTCL reactive oxygen species |
| url | https://www.frontiersin.org/article/10.3389/fonc.2018.00679/full |
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