DOI QR코드

DOI QR Code

Cytotoxic Activities of Amentoflavone against Human Breast and Cervical Cancers are Mediated by Increasing of PTEN Expression Levels due to Peroxisome Proliferator-Activated Receptor γ Activation

  • Lee, Eun-Jung (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Shin, So-Young (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Lee, Jee-Young (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Lee, So-Jung (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Jin-Kyoung (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Yoon, Do-Young (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Woo, Eun-Rhan (College of Pharmacy, Chosun University) ;
  • Kim, Yang-Mee (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University)
  • Received : 2012.03.20
  • Accepted : 2012.03.30
  • Published : 2012.07.20

Abstract

Human peroxisome proliferator-activated receptor gamma ($hPPAR{\gamma}$) has been implicated in numerous pathologies, including obesity, diabetes, and cancer. Previously, we verified that amentoflavone is an activator of $hPPAR{\gamma}$ and probed the molecular basis of its action. In this study, we investigated the mechanism of action of amentoflavone in cancer cells and demonstrated that amentoflavone showed strong cytotoxicity against MCF-7 and HeLa cancer cell lines. We showed that $hPPAR{\gamma}$ expression in MCF-7 and HeLa cells is specifically stimulated by amentoflavone, and suggested that amentoflavone-induced cytotoxic activities are mediated by activation of $hPPAR{\gamma}$ in these two cancer cell lines. Moreover, amentoflavone increased PTEN levels in these two cancer cell lines, indicating that the cytotoxic activities of amentoflavone are mediated by increasing of PTEN expression levels due to $hPPAR{\gamma}$ activation.

Keywords

References

  1. McKenna, N. J.; O'Malley, B. W. Endocrinology 2002, 143, 2461- 2465. https://doi.org/10.1210/en.143.7.2461
  2. Hansen, M. K.; Connolly, T. M. Curr. Opin. Investig. Drugs 2008, 9, 247-255.
  3. Berger, J. P.; Akiyama, T. E.; Meinke, P. T. Trends Pharmacol. Sci. 2005, 26, 244-251. https://doi.org/10.1016/j.tips.2005.03.003
  4. Kersten, S.; Desvergne, B.; Wahli, W. Nature 2000, 405, 421-424. https://doi.org/10.1038/35013000
  5. Berger, J.; Moller, D. E. Annu. Rev. Med. 2002, 53, 409-435. https://doi.org/10.1146/annurev.med.53.082901.104018
  6. Chinetti-Gbaguidi, G.; Fruchart, J. C.; Staels, B. Curr. Opin. Pharmacol. 2005, 5, 177-183. https://doi.org/10.1016/j.coph.2004.11.004
  7. Chinetti, G.; Lestavel, S.; Bocher, V.; Remaley, A. T.; Neve, B.; Torra, I. P.; Teissier, E.; Minnich, A.; Jaye, M.; Duverger, N.; Brewer, H. B.; Fruchart, J. C.; Clavey, V.; Staels, B. Nat. Med. 2001, 7, 53-58. https://doi.org/10.1038/83348
  8. Lee, C. H.; Olson, P.; Evans, R. M. Endocrinology 2003, 144, 2201-2207. https://doi.org/10.1210/en.2003-0288
  9. Bocher, V.; Pineda-Torra, I.; Fruchart, J. C.; Staels, B. Ann. N. Y. Acad. Sci. 2002, 967, 7-18.
  10. Markt, P.; Petersen, R. K.; Flindt, E. N.; Kristiansen, K.; Kirchmair, J.; Spitzer, G.; Distinto, S.; Schuster, D.; Wolber, G.; Laggner, C.; Langer, T. J. Med. Chem. 2008, 51, 6303-63017. https://doi.org/10.1021/jm800128k
  11. Rosen, E. D.; Spiegelman, B. M. J. Biol. Chem. 2001, 276, 37731- 37734. https://doi.org/10.1074/jbc.R100034200
  12. Lehrke, M.; Lazar, M. A. Cell 2005, 123, 993-999. https://doi.org/10.1016/j.cell.2005.11.026
  13. Tontonoz, P.; Spiegelman, B. M. Annu. Rev. Biochem. 2008, 77, 289-312. https://doi.org/10.1146/annurev.biochem.77.061307.091829
  14. Krishnan, A.; Nair, S. A.; Pillai, M. R. Curr. Mol. Med. 2007, 7,532-540. https://doi.org/10.2174/156652407781695765
  15. Steck, P. A.; Pershouse, M. A.; Jasser, S. A.; Yung, W. K.; Lin, H.; Ligon, A. H.; Langford, L. A.; Baumgard, M. L.; Hattier, T.; Davis, T.; Frye, C.; Hu, R.; Swedlund, B.; Teng, D. H.; Tavtigian, S. V. Nat. Genet. 1997, 15, 356-362. https://doi.org/10.1038/ng0497-356
  16. Herpin, A.; Lelong, C.; Favrel, P. Dev. Comp. Immunol. 2004, 28, 461-485. https://doi.org/10.1016/j.dci.2003.09.007
  17. Ye, J. Biochem. Biophys. Res. Commun. 2008, 374, 405-408. https://doi.org/10.1016/j.bbrc.2008.07.068
  18. Cazarolli, L. H.; Zanatta, L.; Alberton, E. H.; Figueiredo, M. S.; Folador, P.; Damazio, R. G.; Pizzolatti, M. G.; Silva, F. R. Mini Rev. Med. Chem. 2008, 8, 1429-1440. https://doi.org/10.2174/138955708786369564
  19. Rajnaryana, K.; Sripalreddy, M.; Chalavadi, M. R.; Krishna, D. R. Indian J. Pharmacol. 2001, 33, 2-16.
  20. Crozier, A.; Jaganath, I. B.; Clifford, M. N. Nat. Prod. Rep. 2009, 26, 1001-1043. https://doi.org/10.1039/b802662a
  21. Butt, M. S.; Sultan, M. T. Crit. Rev. Food Sci. Nutr. 2009, 49, 463- 473. https://doi.org/10.1080/10408390802145310
  22. Manas, E. S.; Xu, Z. B.; Unwalla, R. J.; Somers, W. S. Structure 2004, 12, 2197-2207. https://doi.org/10.1016/j.str.2004.09.015
  23. Lee, J. Y.; Kim, J. K.; Cho, M. C.; Shin, S.; Yoon, D. Y.; Heo, Y. S.; Kim, Y. J. Nat. Prod. 2010, 73, 1261-1265. https://doi.org/10.1021/np100148m
  24. Lee, J. Y.; Jung, K. W.; Woo, E. R.; Kim, Y. Bull. Korean Chem. Soc. 2008, 29, 1479-1484. https://doi.org/10.5012/bkcs.2008.29.8.1479
  25. Lee, J. Y.; Kim, J.-K.; Lee, S.; Lee, E.; Shin, S.; Jin, Q.; Yoon, D.- Y.; Woo, E. R.; Kim, Y. Bull. Korean Chem. Soc. 2012, in press.
  26. Silva, G. L.; Chai, H.; Gupta, M. P.; Farnsworth, N. R.; Cordell, G. A.; Pezzuto, J. M.; Beecher, C. W.; Kinghorn, A. D. Phytochemistry 1995, 40, 129-134. https://doi.org/10.1016/0031-9422(95)00212-P
  27. Lee, H. S.; Cho, M. C.; Paek, T. W.; Choe, Y. K.; Kim, J. W.; Hong, J. T.; Myung, P. K.; Paik, S. G.; Yoon, D. Y. J. Immunol. Methods 2005, 296, 125-134. https://doi.org/10.1016/j.jim.2004.11.011
  28. Banerjee, T.; Valacchi, G.; Ziboh, V. A.; van der Vliet, A. Mol. Cell. Biochem. 2002, 238, 105-110. https://doi.org/10.1023/A:1019963222510
  29. Selvam, C.; Jachak, S. M. J. Ethnopharmacol. 2004, 95, 209-212. https://doi.org/10.1016/j.jep.2004.07.026

Cited by

  1. Gallnuts: A Potential Treasure in Anticancer Drug Discovery vol.2018, pp.1741-4288, 2018, https://doi.org/10.1155/2018/4930371
  2. Flavonoids as Putative Epi-Modulators: Insight into Their Binding Mode with BRD4 Bromodomains Using Molecular Docking and Dynamics vol.8, pp.3, 2018, https://doi.org/10.3390/biom8030061
  3. Anti-inflammatory Activity of 3,6,3'-Trihydroxyflavone in Mouse Macrophages, In vitro vol.35, pp.11, 2014, https://doi.org/10.5012/bkcs.2014.35.11.3169
  4. A new prenylated biflavonoid from the leaves of Garcinia dulcis. vol.29, pp.20, 2015, https://doi.org/10.1080/14786419.2015.1010087
  5. Phospho Tensin Homolog in Human and Lipid Peroxides in Peripheral Blood Mononuclear Cells Following Exposure to Flavonoids vol.39, pp.2, 2012, https://doi.org/10.1080/07315724.2019.1616234