scholarly journals Glycyrrhizin Derivatives Suppress Cancer Chemoresistance by Inhibiting Progesterone Receptor Membrane Component 1

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3265
Author(s):  
Yasuaki Kabe ◽  
Ikko Koike ◽  
Tatsuya Yamamoto ◽  
Miwa Hirai ◽  
Ayaka Kanai ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Cancer Progression ◽  
Egf Receptor ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Human Colon ◽  
Titration Calorimetry ◽  
Membrane Component ◽  
Human Colon Cancer ◽  
Receptor Membrane

Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in various cancer cells and contributes to tumor progression. We have previously shown that PGRMC1 forms a unique heme-stacking functional dimer to enhance EGF receptor (EGFR) activity required for cancer proliferation and chemoresistance, and the dimer dissociates by carbon monoxide to attenuate its biological actions. Here, we determined that glycyrrhizin (GL), which is conventionally used to ameliorate inflammation, specifically binds to heme-dimerized PGRMC1. Binding analyses using isothermal titration calorimetry revealed that some GL derivatives, including its glucoside-derivative (GlucoGL), bind to PGRMC1 potently, whereas its aglycone, glycyrrhetinic acid (GA), does not bind. GL and GlucoGL inhibit the interaction between PGRMC1 and EGFR, thereby suppressing EGFR-mediated signaling required for cancer progression. GL and GlucoGL significantly enhanced EGFR inhibitor erlotinib- or cisplatin (CDDP)-induced cell death in human colon cancer HCT116 cells. In addition, GL derivatives suppressed the intracellular uptake of low-density lipoprotein (LDL) by inhibiting the interaction between PGRMC1 and the LDL receptor (LDLR). Effects on other pathways cannot be excluded. Treatment with GlucoGL and CDDP significantly suppressed tumor growth following xenograft transplantation in mice. Collectively, this study indicates that GL derivatives are novel inhibitors of PGRMC1 that suppress cancer progression, and our findings provide new insights for cancer treatment.

scholarly journals Progesterone receptor membrane associated component 1 enhances obesity progression in mice by facilitating lipid accumulation in adipocytes

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Ryogo Furuhata ◽  
Yasuaki Kabe ◽  
Ayaka Kanai ◽  
Yuki Sugiura ◽  
Hitoshi Tsugawa ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
High Fat Diet ◽  
Metabolic Regulation ◽  
Egf Receptor ◽  
De Novo ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
Lipid Uptake ◽  
High Fat ◽  
Receptor Membrane

AbstractProgesterone receptor membrane associated component 1 (PGRMC1) exhibits haem-dependent dimerization on cell membrane and binds to EGF receptor and cytochromes P450 to regulate cancer proliferation and chemoresistance. However, its physiological functions remain unknown. Herein, we demonstrate that PGRMC1 is required for adipogenesis, and its expression is significantly enhanced by insulin or thiazolidine, an agonist for PPARγ. The haem-dimerized PGRMC1 interacts with low-density lipoprotein receptors (VLDL-R and LDL-R) or GLUT4 to regulate their translocation to the plasma membrane, facilitating lipid uptake and accumulation, and de-novo fatty acid synthesis in adipocytes. These events are cancelled by CO through interfering with PGRMC1 dimerization. PGRMC1 expression in mouse adipose tissues is enhanced during obesity induced by a high fat diet. Furthermore, adipose tissue-specific PGRMC1 knockout in mice dramatically suppressed high-fat-diet induced adipocyte hypertrophy. Our results indicate a pivotal role of PGRMC1 in developing obesity through its metabolic regulation of lipids and carbohydrates in adipocytes.

scholarly journals Correction to: Progesterone receptor membrane component 1 regulates lipid homeostasis and drives oncogenic signaling resulting in breast cancer progression

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Hannah Asperger ◽  
Nadia Stamm ◽  
Berthold Gierke ◽  
Michael Pawlak ◽  
Ute Hofmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Lipid Homeostasis ◽  
Membrane Component ◽  
Oncogenic Signaling ◽  
Receptor Membrane

An amendment to this paper has been published and can be accessed via the original article.

Progesterone receptor membrane component 1 (PGRMC1) expression in canine mammary tumors: A preliminary study

2020 ◽  
Vol 132 ◽  
pp. 101-107
Author(s):  
Laura Terzaghi ◽  
Barbara Banco ◽  
Debora Groppetti ◽  
Priscila C. Dall'Acqua ◽  
Chiara Giudice ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Mammary Tumors ◽  
Membrane Component ◽  
Canine Mammary Tumors ◽  
Receptor Membrane ◽  
Preliminary Study

scholarly journals Progesterone receptor membrane component 1 reduces cardiac steatosis and lipotoxicity via activation of fatty acid oxidation and mitochondrial respiration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sang R. Lee ◽  
Jun H. Heo ◽  
Seong Lae Jo ◽  
Globinna Kim ◽  
Su Jung Kim ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Progesterone Receptor ◽  
Fatty Acid Oxidation ◽  
Mitochondrial Respiration ◽  
De Novo Lipogenesis ◽  
Acid Oxidation ◽  
Membrane Component ◽  
Markers Of Inflammation ◽  
Receptor Membrane

AbstractObesity is implicated in cardiovascular disease and heart failure. When fatty acids are transported to and not adequately oxidized in cardiac cells, they accumulate, causing lipotoxicity in the heart. Since hepatic progesterone receptor membrane component 1 (Pgrmc1) suppressed de novo lipogenesis in a previous study, it was questioned whether cardiac Pgrmc1 protects against lipotoxicity. Hence, we focused on the role of cardiac Pgrmc1 in basal (Resting), glucose-dominant (Refed) and lipid-dominant high-fat diet (HFD) conditions. Pgrmc1 KO mice showed high FFA levels and low glucose levels compared to wild-type (WT) mice. Pgrmc1 KO mice presented low number of mitochondrial DNA copies in heart, and it was concomitantly observed with low expression of TCA cycle genes and oxidative phosphorylation genes. Pgrmc1 absence in heart presented low fatty acid oxidation activity in all conditions, but the production of acetyl-CoA and ATP was in pronounced suppression only in HFD condition. Furthermore, HFD Pgrmc1 KO mice resulted in high cardiac fatty acyl-CoA levels and TG level. Accordingly, HFD Pgrmc1 KO mice were prone to cardiac lipotoxicity, featuring high levels in markers of inflammation, endoplasmic reticulum stress, oxidative stress, fibrosis, and heart failure. In vitro study, it was also confirmed that Pgrmc1 enhances rates of mitochondrial respiration and fatty acid oxidation. This study is clinically important because mitochondrial defects in Pgrmc1 KO mice hearts represent the late phase of cardiac failure.

scholarly journals Roles of Progesterone Receptor Membrane Component 1 in Oxidative Stress–Induced Aging in Chorion Cells

2018 ◽  
Vol 26 (3) ◽  
pp. 394-403 ◽  
Author(s):  
Liping Feng ◽  
Terrence K. Allen ◽  
William P. Marinello ◽  
Amy P. Murtha
Keyword(s):  
Oxidative Stress ◽  
Progesterone Receptor ◽  
Membrane Component ◽  
Receptor Membrane
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