Glycyrrhizin Derivatives Suppress Cancer Chemoresistance by Inhibiting Progesterone Receptor Membrane Component 1
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Antibodies
2.3. Affinity Purification
2.4. Preparation of Plasmid Vectors and Recombinant Proteins
2.5. ITC Analyses
2.6. NMR Analyses
2.7. Hydrogen Deuterium Exchange Mass Spectrometry (HDX-MS)
2.8. Cell Lines and Culture
2.9. Co-Immunoprecipitation Assays
2.10. EGFR Kinase Assay
2.11. Xenograft Implantation of HCT116 Cells
2.12. Statistical Analysis
3. Results
3.1. Identification of PGRMC1 as a Novel GL-Binding Protein
3.2. Binding Structure of GL to Heme-Dimerized PGRMC1
3.3. Binding Analyses Using GL Derivatives
3.4. GL Derivatives Interfere with EGFR Signaling by Inhibiting the Interaction between PGRMC1 and EGFR
3.5. GL Derivatives Interfere with LDL Uptake by Inhibiting the Interaction between PGRMC1 and LDLR
3.6. GL Derivatives Enhance Chemosensitivity in Cancer Cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound | KD (μM) | ΔG (kcal/mol) | ΔH (kcal/mol) | TΔS (K·kcal/mol) | IC 50 (μM) | |
---|---|---|---|---|---|---|
Erlotinib | CDDP | |||||
Glycyrrhizin (GL) | 52.70 | −5.84 | −1.23 | 4.61 | 51.99 | 53.07 |
Glycyrrhetinic acid-3-O-mono-glucuronide | 9.55 | −6.85 | −0.62 | 6.23 | 50.50 | 41.23 |
Licorice-saponin A3 | 16.78 | −6.52 | −1.66 | 4.86 | 40.03 | 39.44 |
Licorice-saponin G2 | 128.50 | −5.31 | −1.23 | 4.08 | ND | ND |
Licorice-saponin H2 | No Binding | ND | ND | |||
Macedonoside A | No Binding | ND | ND | |||
Araboglycyrrhizin | 8.46 | −6.93 | −1.03 | 5.90 | 35.30 | 26.58 |
Apioglycyrrhizin | 4.85 | −7.26 | −1.08 | 6.18 | 62.48 | 35.15 |
Glucoglycyrrhizin (GlucoGL) | 1.38 | −8.00 | −0.56 | 7.44 | 15.67 | 14.92 |
Rhaoglucoglycyrrhizin | 1.08 | −8.15 | −2.07 | 6.08 | 19.05 | 17.25 |
Carbenoxolone | No Binding | ND | ND | |||
Glycyrrhetinic acid (GA) | Weak Binding | ND | ND | |||
Progesterone | 815.60 | −4.22 | −23.26 | −19.04 | ND | ND |
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Kabe, Y.; Koike, I.; Yamamoto, T.; Hirai, M.; Kanai, A.; Furuhata, R.; Tsugawa, H.; Harada, E.; Sugase, K.; Hanadate, K.; et al. Glycyrrhizin Derivatives Suppress Cancer Chemoresistance by Inhibiting Progesterone Receptor Membrane Component 1. Cancers 2021, 13, 3265. https://doi.org/10.3390/cancers13133265
Kabe Y, Koike I, Yamamoto T, Hirai M, Kanai A, Furuhata R, Tsugawa H, Harada E, Sugase K, Hanadate K, et al. Glycyrrhizin Derivatives Suppress Cancer Chemoresistance by Inhibiting Progesterone Receptor Membrane Component 1. Cancers. 2021; 13(13):3265. https://doi.org/10.3390/cancers13133265
Chicago/Turabian StyleKabe, Yasuaki, Ikko Koike, Tatsuya Yamamoto, Miwa Hirai, Ayaka Kanai, Ryogo Furuhata, Hitoshi Tsugawa, Erisa Harada, Kenji Sugase, Kazue Hanadate, and et al. 2021. "Glycyrrhizin Derivatives Suppress Cancer Chemoresistance by Inhibiting Progesterone Receptor Membrane Component 1" Cancers 13, no. 13: 3265. https://doi.org/10.3390/cancers13133265