AUTHOR=Zhou Lixia , Yu Tenghua , Yang Fei , Han Jingjing , Zuo Bin , Huang Lulu , Bai Xia , Jiang Miao , Wu Depei , Chen Suning , Xia Lijun , Ruan Jia , Ruan Changgeng TITLE=G Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Mantle Cell Lymphoma Growth in Preclinical Models JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.668617 DOI=10.3389/fonc.2021.668617 ISSN=2234-943X 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.