The Korean Journal of Physiology and Pharmacology

  • 제28권4호
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  • Pages.379-387
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  • 2024
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  • 1226-4512(pISSN)
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  • 2093-3827(eISSN)
대한약리학회 (The Korean Society of Pharmacology)
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Polygonatum sibiricum component liquiritigenin restrains breast cancer cell invasion and migration by inhibiting HSP90 and chaperone-mediated autophagy

  • Suli Xu (Department of Medicine, Huangshan Vocational Technical College) ;
  • Zhao Ma (Department of Medicine, Huangshan Vocational Technical College) ;
  • Lihua Xing (School of Pharmacy, Anhui University of Chinese Medicine) ;
  • Weiqing Cheng (Department of Pharmacy, Fujian Vocational College of Bioengineering)
  • 투고 : 2024.01.03
  • 심사 : 2024.03.13
  • 발행 : 2024.07.01
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초록

Breast cancer (BC) is most commonly diagnosed worldwide. Liquiritigenin is a flavonoid found in various species of the Glycyrrhiza genus, showing anti-tumor activity. This article was to explore the influences of liquiritigenin on the biological behaviors of BC cells and its underlying mechanism. BC cells were treated with liquiritigenin alone or transfected with oe-HSP90 before liquiritigenin treatment. RT-qPCR and Western blotting were employed to examine the levels of HSP90, Snail, E-cadherin, HSC70, and LAMP-2A. Cell viability, proliferation, migration, and invasion were evaluated by performing MTT, colony formation, scratch, and Transwell assays, respectively. Liquiritigenin treatment reduced HSP90 and Snail levels and enhanced E-cadherin expression as well as inhibiting the proliferation, migration, and invasion of BC cells. Moreover, liquiritigenin treatment decreased the expression of HSC70 and LAMP-2A, proteins related to chaperone-mediated autophagy (CMA). HSP90 overexpression promoted the CMA, invasion, and migration of BC cells under liquiritigenin treatment. Liquiritigenin inhibits HSP90-mediated CMA, thereby suppressing BC cell growth.

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과제정보

Thanks for the grants from the Anhui University Natural Science Key Project in 2021 (No. KJ2021A1441) and Anhui Quality Engineering Project in 2021 (No. 2021cjrh047).

참고문헌

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209-249.  https://doi.org/10.3322/caac.21660
  2. Barzaman K, Karami J, Zarei Z, Hosseinzadeh A, Kazemi MH, Moradi-Kalbolandi S, Safari E, Farahmand L. Breast cancer: biology, biomarkers, and treatments. Int Immunopharmacol. 2020;84:106535. 
  3. Britt KL, Cuzick J, Phillips KA. Key steps for effective breast cancer prevention. Nat Rev Cancer. 2020;20:417-436.  https://doi.org/10.1038/s41568-020-0266-x
  4. Liang Y, Zhang H, Song X, Yang Q. Metastatic heterogeneity of breast cancer: molecular mechanism and potential therapeutic targets. Semin Cancer Biol. 2020;60:14-27.  https://doi.org/10.1016/j.semcancer.2019.08.012
  5. Wahab S, Annadurai S, Abullais SS, Das G, Ahmad W, Ahmad MF, Kandasamy G, Vasudevan R, Ali MS, Amir M. Glycyrrhiza glabra (Licorice): a comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicology. Plants (Basel). 2021;10:2751. 
  6. Zhou M, Dai Y, Ma Y, Yan Y, Hua M, Gao Q, Geng X, Zhou Q. Protective effects of liquiritigenin against cisplatin-induced nephrotoxicity via NRF2/SIRT3-mediated improvement of mitochondrial function. Molecules. 2022;27:3823. 
  7. Zhang M, Xue Y, Zheng B, Li L, Chu X, Zhao Y, Wu Y, Zhang J, Han X, Wu Z, Chu L. Liquiritigenin protects against arsenic trioxide-induced liver injury by inhibiting oxidative stress and enhancing mTOR-mediated autophagy. Biomed Pharmacother. 2021;143:112167. 
  8. Li L, Fang H, Yu YH, Liu SX, Yang ZQ. Liquiritigenin attenuates isoprenalineinduced myocardial fibrosis in mice through the TGFβ1/Smad2 and AKT/ERK signaling pathways. Mol Med Rep. 2021;24:686. 
  9. Wang D, Wong HK, Feng YB, Zhang ZJ. Liquiritigenin exhibits antitumour action in pituitary adenoma cells via Ras/ERKs and ROS-dependent mitochondrial signalling pathways. J Pharm Pharmacol. 2014;66:408-417.  https://doi.org/10.1111/jphp.12170
  10. Wang D, Lu J, Liu Y, Meng Q, Xie J, Wang Z, Teng L. Liquiritigenin induces tumor cell death through mitogen-activated protein kinase-(MPAKs-) mediated pathway in hepatocellular carcinoma cells. Biomed Res Int. 2014;2014:965316. 
  11. Zhang Z, Lin J, Hu J, Liu L. Liquiritigenin blocks breast cancer progression by inhibiting connective tissue growth factor expression via up-regulating miR-383-5p. Int J Toxicol. 2022;41:5-15.  https://doi.org/10.1177/10915818211059470
  12. Liang Y, Besch-Williford C, Hyder SM. The estrogen receptor beta agonist liquiritigenin enhances the inhibitory effects of the cholesterol biosynthesis inhibitor RO 48-8071 on hormone-dependent breast-cancer growth. Breast Cancer Res Treat. 2022;192:53-63.  https://doi.org/10.1007/s10549-021-06487-y
  13. Liang F, Zhang H, Gao H, Cheng D, Zhang N, Du J, Yue J, Du P, Zhao B, Yin L. Liquiritigenin decreases tumorigenesis by inhibiting DNMT activity and increasing BRCA1 transcriptional activity in triple-negative breast cancer. Exp Biol Med (Maywood). 2021;246:459-466.  https://doi.org/10.1177/1535370220957255
  14. Lei S, Fan P, Wang M, Zhang C, Jiang Y, Huang S, Fang M, He Z, Wu A. Elevated estrogen receptor E expression in triple negative breast cancer cells is associated with sensitivity to doxorubicin by inhibiting the PI3K/AKT/mTOR signaling pathway. Exp Ther Med. 2020;20:1630-1636.  https://doi.org/10.3892/etm.2020.8809
  15. Alberti G, Vergilio G, Paladino L, Barone R, Cappello F, Conway de Macario E, Macario AJL, Bucchieri F, Rappa F. The chaperone system in breast cancer: roles and therapeutic prospects of the molecular chaperones Hsp27, Hsp60, Hsp70, and Hsp90. Int J Mol Sci. 2022;23:7792. 
  16. Birbo B, Madu EE, Madu CO, Jain A, Lu Y. Role of HSP90 in cancer. Int J Mol Sci. 2021;22:10317. 
  17. Zhang PC, Liu X, Li MM, Ma YY, Sun HT, Tian XY, Wang Y, Liu M, Fu LS, Wang YF, Chen HY, Liu Z. AT-533, a novel Hsp90 inhibitor, inhibits breast cancer growth and HIF-1D/VEGF/VEGFR2-mediated angiogenesis in vitro and in vivo. Biochem Pharmacol. 2020;172:113771. 
  18. Yang F, Sun R, Hou Z, Zhang FL, Xiao Y, Yang YS, Yang SY, Xie YF, Liu YY, Luo C, Liu GY, Shao ZM, Li DQ. HSP90 N-terminal inhibitors target oncoprotein MORC2 for autophagic degradation and suppress MORC2-driven breast cancer progression. Clin Transl Med. 2022;12:e825. 
  19. Kale S, Korcum AF, Dundar E, Erin N. HSP90 inhibitor PU-H71 increases radiosensitivity of breast cancer cells metastasized to visceral organs and alters the levels of inflammatory mediators. Naunyn Schmiedebergs Arch Pharmacol. 2020;393:253-262.  https://doi.org/10.1007/s00210-019-01725-z
  20. Hubert V, Weiss S, Rees AJ, Kain R. Modulating chaperone-mediated autophagy and its clinical applications in cancer. Cells. 2022;11:2562. 
  21. Su CM, Hsu TW, Chen HA, Wang WY, Huang CY, Hung CC, Yeh MH, Su YH, Huang MT, Liao PH. Chaperone-mediated autophagy degrade Dicer to promote breast cancer metastasis. J Cell Physiol. 2023;238:829-841. 
  22. Chen R, Li P, Fu Y, Wu Z, Xu L, Wang J, Chen S, Yang M, Peng B, Yang Y, Zhang H, Han Q, Li S. Chaperone-mediated autophagy promotes breast cancer angiogenesis via regulation of aerobic glycolysis. PLoS One. 2023;18:e0281577. 
  23. Chen H, Li S, Yin H, Hua Z, Shao Y, Wei J, Wang J. MYC-mediated miR-320a affects receptor activator of nuclear factor NB ligand (RANKL)-induced osteoclast formation by regulating phosphatase and tensin homolog (PTEN). Bioengineered. 2021;12:12677-12687.  https://doi.org/10.1080/21655979.2021.2008666
  24. Soejima M, Koda Y. TaqMan-based real-time PCR for genotyping common polymorphisms of haptoglobin (HP1 and HP2). Clin Chem. 2008;54:1908-1913.  https://doi.org/10.1373/clinchem.2008.113126
  25. Wilkinson L, Gathani T. Understanding breast cancer as a global health concern. Br J Radiol. 2022;95:20211033. 
  26. Meng FC, Lin JK. Liquiritigenin inhibits colorectal cancer proliferation, invasion, and epithelial-to-mesenchymal transition by decreasing expression of runt-related transcription factor 2. Oncol Res. 2019;27:139-146.  https://doi.org/10.3727/096504018X15185747911701
  27. Ji Y, Hu W, Jin Y, Yu H, Fang J. Liquiritigenin exerts the anticancer role in oral cancer via inducing autophagy-related apoptosis through PI3K/AKT/mTOR pathway inhibition in vitro and in vivo. Bioengineered. 2021;12:6070-6082.  https://doi.org/10.1080/21655979.2021.1971501
  28. Asberger J, Erbes T, Jaeger M, Rucker G, Nothling C, Ritter A, Berner K, Juhasz-Boss I, Hirschfeld M. Endoxifen and fulvestrant regulate estrogen-receptor D and related DEADbox proteins. Endocr Connect. 2020;9:1156-1167.  https://doi.org/10.1530/EC-20-0281
  29. Wang D, Wang Y, Wu X, Kong X, Li J, Dong C. RNF20 is critical for Snail-mediated E-cadherin repression in human breast cancer. Front Oncol. 2020;10:613470. 
  30. Park S, Kim YJ, Park JM, Park M, Nam KD, Farrand L, Nguyen CT, La MT, Ann J, Lee J, Kim JY, Seo JH. The C-terminal HSP90 inhibitor NCT-58 kills trastuzumab-resistant breast cancer stem-like cells. Cell Death Discov. 2021;7:354. 
  31. Park JM, Kim YJ, Park S, Park M, Farrand L, Nguyen CT, Ann J, Nam G, Park HJ, Lee J, Kim JY, Seo JH. A novel HSP90 inhibitor targeting the C-terminal domain attenuates trastuzumab resistance in HER2-positive breast cancer. Mol Cancer. 2020;19:161. 
  32. Rahmy S, Mishra SJ, Murphy S, Blagg BSJ, Lu X. Hsp90E inhibition upregulates interferon response and enhances immune checkpoint blockade therapy in murine tumors. Front Immunol. 2022;13:1005045. 
  33. Bouchard A, Sikner H, Baverel V, Garnier AR, Monterrat M, Moreau M, Limagne E, Garrido C, Kohli E, Collin B, Bellaye PS. The GRP94 inhibitor PU-WS13 decreases M2-like macrophages in murine TNBC tumors: a pharmaco-imaging study with 99mTc-Tilmanocept SPECT. Cells. 2021;10:3393. 
  34. Li ZN, Luo Y. HSP90 inhibitors and cancer: prospects for use in targeted therapies (review). Oncol Rep. 2023;49:6. 
  35. Assaye MA, Gizaw ST. Chaperone-mediated autophagy and its implications for neurodegeneration and cancer. Int J Gen Med. 2022;15:5635-5649. https://doi.org/10.2147/IJGM.S368364