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Anti-metastatic Effect of Natural Product-motivated Synthetic PPAR-γ Ligands

  • Li, Dan-dan (College of Pharmacy, Pusan National University) ;
  • Wang, Ying (College of Pharmacy, Pusan National University) ;
  • Ju, Zhiran (College of Pharmacy, Pusan National University) ;
  • Kim, Eun La (College of Pharmacy, Pusan National University) ;
  • Hong, Jongki (College of Pharmacy, Kyung Hee University) ;
  • Jung, Jee H. (College of Pharmacy, Pusan National University)
  • Received : 2022.05.11
  • Accepted : 2022.06.23
  • Published : 2022.06.30

Abstract

Colorectal cancer is one of the most common cancers globally, ranking second for the number of cancer-related deaths. Metastasis has been reported as the main cause of death in patients with colorectal cancer. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a transcription factor that functions as a tumor suppressor by inhibiting cellular proliferation, migration, and invasion. In our previous efforts to generate natural product-motivated PPAR-γ ligands, the compounds 1 and 2 were obtained. These compounds activated PPAR-γ and inhibited the migration and invasion of HCT116 colorectal cancer cells, and they were also found to inhibit the epithelial-to-mesenchymal transition, which is a key process in cancer metastasis. Compounds 1 and 2 upregulated expression of the epithelial marker (E-cadherin), and downregulated expression of the mesenchymal marker (N-cadherin) and transcriptional factor (Snail). Therefore, the PPAR-γ agonists 1 and 2 could serve as a valuable model for the study on anti-metastatic leads for the treatment of colorectal cancer.

Keywords

Acknowledgement

This research was supported by a 2-year grant from Pusan National University.

References

  1. Siegel, R. L.; Miller, K. D.; Goding Sauer, A.; Fedewa, S. A.; Butterly, L. F.; Anderson, J. C.; Cercek, A.; Smith, R. A.; Jemal, A. CA Cancer J. Clin. 2020, 70, 145-164. https://doi.org/10.3322/caac.21601
  2. Cartwright, T. H. Clin. Colorectal Cancer 2012, 11, 155-166. https://doi.org/10.1016/j.clcc.2011.11.001
  3. Kamiyama, H.; Noda, H.; Konishi, F.; Rikiyama, T. World J. Gastroenterol. 2014, 20, 8928-8938. https://doi.org/10.3748/wjg.v20.i27.8928
  4. Wanebo, H. J.; LeGolvan, M.; Paty, P. B.; Saha, S.; Zuber, M.; D'Angelica, M. I.; Kemeny, N. E. Clin. Exp. Metastasis. 2012, 29, 821-839. https://doi.org/10.1007/s10585-012-9517-x
  5. Li, C.; Wang, J.; Kong, J.; Tang, J.; Wu, Y.; Xu, E.; Zhang, H.; Lai, M. Oncotarget 2016, 7, 860-872. https://doi.org/10.18632/oncotarget.6205
  6. Nieto, M. A.; Huang, R. Y.; Jackson, R. A.; Thiery, J. P. Cell 2016, 166, 21-45. https://doi.org/10.1016/j.cell.2016.06.028
  7. Lu, H. Y.; Chu, H. X.; Tan, Y. X.; Qin, X. C.; Liu, M. Y.; Li, J. D.; Ren, T. S.; Zhang, Y. S.; Zhao, Q. C. Life Sci. 2020, 244, 117343. https://doi.org/10.1016/j.lfs.2020.117343
  8. Gloushankova, N. A.; Zhitnyak, I. Y.; Rubtsova, S. N. Biochemistry 2018, 83, 1469-1476. https://doi.org/10.1134/s0006297918120052
  9. Vu, T.; Datta, P. K. Cancers 2017, 9, 171. https://doi.org/10.3390/cancers9120171
  10. Yousefnia, S.; Momenzadeh, S.; Seyed Forootan, F.; Ghaedi, K.; Nasr Esfahani, M. H. Gene 2018, 649, 14-22. https://doi.org/10.1016/j.gene.2018.01.018
  11. Elstner, E.; Muller, C.; Koshizuka, K.; Williamson, E. A.; Park, D.; Asou, H.; Shintaku, P.; Said, J. W.; Heber, D.; Koeffler, H. P. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 8806-8811. https://doi.org/10.1073/pnas.95.15.8806
  12. Tsubouchi, Y.; Sano, H.; Kawahito, Y.; Mukai, S.; Yamada, R.; Kohno, M.; Inoue, K.; Hla, T.; Kondo, M. Biochem. Biophys. Res. Commun. 2000, 270, 400-405. https://doi.org/10.1006/bbrc.2000.2436
  13. Kitamura, S.; Miyazaki, Y.; Shinomura, Y.; Kondo, S.; Kanayama, S.; Matsuzawa, Y. Jpn. J. Cancer Res. 1999, 90, 75-80. https://doi.org/10.1111/j.1349-7006.1999.tb00668.x
  14. Ninomiya, I.; Yamazaki, K.; Oyama, K.; Hayashi, H.; Tajima, H.; Kitagawa, H.; Fushida, S.; Fujimura, T.; Ohta, T. Oncol. Lett. 2014, 8, 2709-2714. https://doi.org/10.3892/ol.2014.2553
  15. Su, M.; Cao, J.; Huang, J.; Liu, S.; Im, D. S.; Yoo, J. W.; Jung, J. H. Mar. Drugs 2017, 15, 7. https://doi.org/10.3390/md15010007
  16. Shu, L.; Huang, R.; Wu, S.; Chen, Z.; Sun, K.; Jiang, Y.; Cai, X. Curr. Stem Cell Res. Ther. 2016, 11, 274-281. https://doi.org/10.2174/1574888X10666150630111618
  17. Chang, S. N.; Lee, J. M.; Oh, H.; Kim, U.; Ryu, B.; Park, J. H. Oncol. Lett. 2018, 16, 5482-5488. https://doi.org/10.3892/ol.2018.9278
  18. Magenta, G.; Borenstein, X.; Rolando, R.; Jasnis, M. A. BMC cancer 2008, 8, 47. https://doi.org/10.1186/1471-2407-8-47
  19. Wei, J.; Li, Z.; Yuan, F. Cell Biol. Int. 2014, 38, 875-880. https://doi.org/10.1002/cbin.10270
  20. Choudhary, R.; Li, H.; Winn, R. A.; Sorenson, A. L.; Weiser-Evans, M. C.; Nemenoff, R. A. Neoplasia. 2010, 12, 224-234. https://doi.org/10.1593/neo.91638
  21. Cai, W.; Yang, T.; Liu, H.; Han, L.; Zhang, K.; Hu, X.; Zhang, X.; Yin, K. J.; Gao, Y.; Bennett, M. V. L.; Leak, R. K.; Chen, J. Prog. Neurobiol. 2018, 163-164, 27-58. https://doi.org/10.1016/j.pneurobio.2017.10.002
  22. Forman, B. M.; Tontonoz, P.; Chen, J.; Brun, R. P.; Spiegelman, B. M.; Evans, R. M. Cell 1995, 83, 803-812. https://doi.org/10.1016/0092-8674(95)90193-0
  23. Li, J.; Guo, C.; Wu, J. PPAR Res. 2019, 2019, 7242030.
  24. Ju, Z.; Su, M.; Hong, J.; Kim, E. L.; Jung, J. H. Bioorg. Chem. 2020, 96, 103611. https://doi.org/10.1016/j.bioorg.2020.103611
  25. Ju, Z.; Su, M.; Hong, J.; Ullah, S.; Kim, E. L.; Zhao, C. H.; Moon, H. R.; Kim, S.; Jung, J. H. Eur. J. Med. Chem. 2018, 157, 1192-1201. https://doi.org/10.1016/j.ejmech.2018.08.090
  26. Tahtamouni, L.; Ahram, M.; Koblinski, J.; Rolfo, C. Anal. Cell Pathol. 2019, 2019, 1356508. https://doi.org/10.1155/2019/1356508
  27. Krakhmal, N. V.; Zavyalova, M. V.; Denisov, E. V.; Vtorushin, S. V.; Perelmuter, V. M. Acta Naturae 2015, 7, 17-28. https://doi.org/10.32607/20758251-2015-7-2-17-28
  28. Pijuan, J.; Barcelo, C.; Moreno, D. F.; Maiques, O.; Siso, P.; Marti, R. M.; Macia, A.; Panosa, A. Front. Cell Dev. Biol. 2019, 7, 107. https://doi.org/10.3389/fcell.2019.00107
  29. Mos hawih, S.; Cheema, M. S.; Ibraheem, Z. O.; Tailan, N. D.; Hakim, M. N. Porto. Biomed. J. 2017, 2, 293-300. https://doi.org/10.1016/j.pbj.2017.03.008
  30. Franken, N. A.; Rodermond, H. M.; Stap, J.; Haveman, J.; van Bree, C. Nat. Protoc. 2006, 1, 2315-2319. https://doi.org/10.1038/nprot.2006.339
  31. Su, M.; Zhao, C.; Li, D.; Cao, J.; Ju, Z.; Kim, E. L.; Jung, Y. S.; Jung, J. H. Mar. Drugs 2020, 18, 445. https://doi.org/10.3390/md18090445
  32. Vodenkova, S.; Buchler, T.; Cervena, K.; Veskrnova, V.; Vodicka, P.; Vymetalkova, V. Pharmacol. Ther. 2020, 206, 107447. https://doi.org/10.1016/j.pharmthera.2019.107447
  33. Zhu, Y.; Wang, C.; Becker, S. A.; Hurst, K.; Nogueira, L. M.; Findlay, V. J.; Camp, E. R. Mol. Ther. 2018, 26, 744-754. https://doi.org/10.1016/j.ymthe.2017.12.023
  34. Mendonsa, A. M.; Na, T. Y.; Gumbiner, B. M. Oncogene 2018, 37, 4769-4780. https://doi.org/10.1038/s41388-018-0304-2
  35. Sommariva, M.; Gagliano, N. Cells 2020, 9, 1040. https://doi.org/10.3390/cells9041040
  36. Padmanaban, V.; Krol, I.; Suhail, Y.; Szczerba, B. M.; Aceto, N.; Bader, J. S.; Ewald, A. J. Nature 2019, 573, 439-444. https://doi.org/10.1038/s41586-019-1526-3
  37. Loh, C. Y.; Chai, J. Y.; Tang, T. F.; Wong, W. F.; Sethi, G.; Shanmugam, M. K.; Chong, P. P.; Looi, C. Y. Cells 2019, 8, 1118. https://doi.org/10.3390/cells8101118
  38. Nemenoff, R. A.; Weiser-Evans, M.; Winn, R. A. PPAR Res. 2008, 2008, 156875. https://doi.org/10.1155/2008/156875
  39. Batlle, E.; Sancho, E.; Franci, C.; Dominguez, D.; Monfar, M.; Baulida, J.; Garcia De Herreros, A. Nat. Cell Biol. 2000, 2, 84-89. https://doi.org/10.1038/35000034
  40. Comijn, J.; Berx, G.; Vermassen, P.; Verschueren, K.; van Grunsven, L.; Bruyneel, E.; Mareel, M.; Huylebroeck, D.; van Roy, F. Mol. Cell 2001, 7, 1267-1278. https://doi.org/10.1016/S1097-2765(01)00260-X