Preclinical Evaluation of the HDAC Inhibitor Chidamide in Transformed Follicular Lymphoma
The key factors leading to transformed follicular lymphoma (t-FL) include the aberrations of epigenetic modifiers as early and driving events, especially mutations in the gene encoding for histone acetyltransferase. Therefore, reversal of this phenomenon by histone deacetylase (HDAC) inhibitors is e...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-12-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.780118/full |
| _version_ | 1830199594658562048 |
|---|---|
| author | Mengya Zhong Mengya Zhong Jinshui Tan Jinshui Tan Guangchao Pan Guangchao Pan Yuelong Jiang Yuelong Jiang Hui Zhou Hui Zhou Qian Lai Qian Lai Qinwei Chen Qinwei Chen Liyuan Fan Liyuan Fan Manman Deng Manman Deng Bing Xu Bing Xu Jie Zha Jie Zha |
| author_facet | Mengya Zhong Mengya Zhong Jinshui Tan Jinshui Tan Guangchao Pan Guangchao Pan Yuelong Jiang Yuelong Jiang Hui Zhou Hui Zhou Qian Lai Qian Lai Qinwei Chen Qinwei Chen Liyuan Fan Liyuan Fan Manman Deng Manman Deng Bing Xu Bing Xu Jie Zha Jie Zha |
| author_sort | Mengya Zhong |
| collection | DOAJ |
| description | The key factors leading to transformed follicular lymphoma (t-FL) include the aberrations of epigenetic modifiers as early and driving events, especially mutations in the gene encoding for histone acetyltransferase. Therefore, reversal of this phenomenon by histone deacetylase (HDAC) inhibitors is essential for the development of new treatment strategies in t-FL. Several t-FL cell lines were treated with various doses of chidamide and subjected to cell proliferation, apoptosis and cell cycle analyses with CCK-8 assay, Annexin V/PI assay and flow cytometry, respectively. Chidamide dose-dependently inhibited cell proliferation, caused G0/G1 cycle arrest and triggered apoptosis in t-FL cells. In addition, the effects of chidamide on tumor growth were evaluated in vivo in xenograft models. RNA-seq analysis revealed gene expression alterations involving the PI3K-AKT signaling pathway might account for the mechanism underlying the antitumor activity of chidamide as a single agent in t-FL. These findings provide a basis for further clinical exploration of chidamide as a promising treatment for FL. |
| first_indexed | 2024-12-18T02:15:39Z |
| format | Article |
| id | doaj.art-3d713885de444a33b83a276132d8180e |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-18T02:15:39Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-3d713885de444a33b83a276132d8180e2022-12-21T21:24:22ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-12-011110.3389/fonc.2021.780118780118Preclinical Evaluation of the HDAC Inhibitor Chidamide in Transformed Follicular LymphomaMengya Zhong0Mengya Zhong1Jinshui Tan2Jinshui Tan3Guangchao Pan4Guangchao Pan5Yuelong Jiang6Yuelong Jiang7Hui Zhou8Hui Zhou9Qian Lai10Qian Lai11Qinwei Chen12Qinwei Chen13Liyuan Fan14Liyuan Fan15Manman Deng16Manman Deng17Bing Xu18Bing Xu19Jie Zha20Jie Zha21Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Hematology, Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy, Xiamen, ChinaDepartment of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Hematology, Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy, Xiamen, ChinaDepartment of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Hematology, Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy, Xiamen, ChinaDepartment of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Hematology, Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy, Xiamen, ChinaDepartment of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Hematology, Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy, Xiamen, ChinaDepartment of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Hematology, Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy, Xiamen, ChinaDepartment of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Hematology, Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy, Xiamen, ChinaDepartment of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Hematology, Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy, Xiamen, ChinaDepartment of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Hematology, Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy, Xiamen, ChinaDepartment of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Hematology, Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy, Xiamen, ChinaDepartment of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Hematology, Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy, Xiamen, ChinaThe key factors leading to transformed follicular lymphoma (t-FL) include the aberrations of epigenetic modifiers as early and driving events, especially mutations in the gene encoding for histone acetyltransferase. Therefore, reversal of this phenomenon by histone deacetylase (HDAC) inhibitors is essential for the development of new treatment strategies in t-FL. Several t-FL cell lines were treated with various doses of chidamide and subjected to cell proliferation, apoptosis and cell cycle analyses with CCK-8 assay, Annexin V/PI assay and flow cytometry, respectively. Chidamide dose-dependently inhibited cell proliferation, caused G0/G1 cycle arrest and triggered apoptosis in t-FL cells. In addition, the effects of chidamide on tumor growth were evaluated in vivo in xenograft models. RNA-seq analysis revealed gene expression alterations involving the PI3K-AKT signaling pathway might account for the mechanism underlying the antitumor activity of chidamide as a single agent in t-FL. These findings provide a basis for further clinical exploration of chidamide as a promising treatment for FL.https://www.frontiersin.org/articles/10.3389/fonc.2021.780118/fulltransformed-follicular lymphoma (t-FL)chidamideHDACPI3K/AKT signalingepigenetic antitumor therapy |
| spellingShingle | Mengya Zhong Mengya Zhong Jinshui Tan Jinshui Tan Guangchao Pan Guangchao Pan Yuelong Jiang Yuelong Jiang Hui Zhou Hui Zhou Qian Lai Qian Lai Qinwei Chen Qinwei Chen Liyuan Fan Liyuan Fan Manman Deng Manman Deng Bing Xu Bing Xu Jie Zha Jie Zha Preclinical Evaluation of the HDAC Inhibitor Chidamide in Transformed Follicular Lymphoma Frontiers in Oncology transformed-follicular lymphoma (t-FL) chidamide HDAC PI3K/AKT signaling epigenetic antitumor therapy |
| title | Preclinical Evaluation of the HDAC Inhibitor Chidamide in Transformed Follicular Lymphoma |
| title_full | Preclinical Evaluation of the HDAC Inhibitor Chidamide in Transformed Follicular Lymphoma |
| title_fullStr | Preclinical Evaluation of the HDAC Inhibitor Chidamide in Transformed Follicular Lymphoma |
| title_full_unstemmed | Preclinical Evaluation of the HDAC Inhibitor Chidamide in Transformed Follicular Lymphoma |
| title_short | Preclinical Evaluation of the HDAC Inhibitor Chidamide in Transformed Follicular Lymphoma |
| title_sort | preclinical evaluation of the hdac inhibitor chidamide in transformed follicular lymphoma |
| topic | transformed-follicular lymphoma (t-FL) chidamide HDAC PI3K/AKT signaling epigenetic antitumor therapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.780118/full |
| work_keys_str_mv | AT mengyazhong preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT mengyazhong preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT jinshuitan preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT jinshuitan preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT guangchaopan preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT guangchaopan preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT yuelongjiang preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT yuelongjiang preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT huizhou preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT huizhou preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT qianlai preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT qianlai preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT qinweichen preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT qinweichen preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT liyuanfan preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT liyuanfan preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT manmandeng preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT manmandeng preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT bingxu preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT bingxu preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT jiezha preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma AT jiezha preclinicalevaluationofthehdacinhibitorchidamideintransformedfollicularlymphoma |