Frontiers in Oncology (Jun 2021)
G Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Mantle Cell Lymphoma Growth in Preclinical Models
- Lixia Zhou,
- Lixia Zhou,
- Tenghua Yu,
- Fei Yang,
- Jingjing Han,
- Bin Zuo,
- Lulu Huang,
- Xia Bai,
- Xia Bai,
- Xia Bai,
- Xia Bai,
- Miao Jiang,
- Depei Wu,
- Depei Wu,
- Suning Chen,
- Suning Chen,
- Lijun Xia,
- Lijun Xia,
- Jia Ruan,
- Changgeng Ruan,
- Changgeng Ruan,
- Changgeng Ruan,
- Changgeng Ruan
Affiliations
- Lixia Zhou
- Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, China
- Lixia Zhou
- Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Tenghua Yu
- Department of Breast Surgery, Jiangxi Cancer Hospital, Nanchang, China
- Fei Yang
- Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, China
- Jingjing Han
- Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, China
- Bin Zuo
- Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, China
- Lulu Huang
- Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, China
- Xia Bai
- Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, China
- Xia Bai
- Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Xia Bai
- Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States
- Xia Bai
- State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China
- Miao Jiang
- Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, China
- Depei Wu
- Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, China
- Depei Wu
- Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Suning Chen
- Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, China
- Suning Chen
- Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Lijun Xia
- Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, China
- Lijun Xia
- Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States
- Jia Ruan
- Division of Hematology and Medical Oncology, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, United States
- Changgeng Ruan
- Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, China
- Changgeng Ruan
- Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
- Changgeng Ruan
- Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States
- Changgeng Ruan
- State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China
- DOI
- https://doi.org/10.3389/fonc.2021.668617
- Journal volume & issue
-
Vol. 11
Abstract
Mantle cell lymphoma (MCL) is an aggressive form of non-Hodgkin’s B-cell lymphoma with poor prognosis. Despite recent advances, resistance to therapy and relapse remain significant clinical problems. G-protein-coupled estrogen receptor (GPER)-mediated estrogenic rapid signaling is implicated in the development of many cancers. However, its role in MCL is unknown. Here we report that GPER activation with selective agonist G-1 induced cell cycle arrest, DNA damage, mitochondria membrane potential abnormality, and eventually apoptosis of MCL cell lines. We found that G-1 induced DNA damage and apoptosis of MCL cells by promoting the expression of nicotinamide adenine dinucleotide phosphate oxidase and the generation of reactive oxygen species. In addition, G-1 inhibited MCL cell proliferation by inactivation of NF-κB signaling and exhibited anti-tumor functions in MCL xenografted mice. Most significantly, G-1 showed synergistic effect with ibrutinib making it a potential candidate for chemotherapy-free therapies against MCL.
Keywords
- Mantle cell lymphoma
- G protein-coupled estrogen receptor (GPER)
- G-1
- cell proliferation
- apoptosis
- chemotherapy-free strategies
