JOURNAL OF CHILEAN CHEMICAL SOCIETY

Vol 64 No 2 (2019): Journal of the Chilean Chemical Society
Original Research Papers

ENHANCEMENT OF CYTOTOXIC ACTIVITY BY ENCAPSULATION IN PLURONIC POLYMER MICELLES: LEPTOCARPHA RIVULARIS EXTRACTS AGAINST HUMAN CANCER CELL LINES

Andrés F. Olea
Instituto de Ciencias Químicas Aplicadas, Facultad de Ingeniería, Universidad Autónoma de Chile
Joan Villena
Centro de Investigaciones Biomédicas (CIB) , Escuela de Medicina, Universidad de Valparaíso
Alejandra Moller
Escuela de Tecnología Médica, Universidad de Valparaíso
Rolando Martínez
Departamento de Química, Facultad de Ciencias Exactas, Universidad Andrés Bello,
Héctor Carrasco
Instituto de Ciencias Químicas Aplicadas, Facultad de Ingeniería, Universidad Autónoma de Chile
Published July 25, 2019
Keywords
  • Cytotoxicity,
  • plant extracts,
  • sesquiterpene lactones,
  • leptocarpine,
  • apoptosis,
  • polymer micelles
  • ...More
    Less

Abstract

Leptocarpha rivularis is an autochthonous plant of the southern zone of Chile known as Palo negro that has been traditionally used by Mapuche people as antiinflammatory and reliever of abdominal pain. More recently, aqueous infusion of this plant is being used in the treatment of cancer. The main phytochemical components of L. rivularis have been identified as a sesquiterpene lactones (SQL) being leptocarpine (LTC) the major component, which exhibits pro-apoptotic action against a variety of cancer cells lines. In this study we intend to compare the in vitro cytotoxicity against cancer cell lines of two different polarity extracts and LTC. To overcome the poor water-solubility of extracts they have been encapsulated in polymer micelles and its effect on activity has been assessed.

The results indicate that both extracts reduce cell viability of all cancer cell lines. The IC50 values obtained for ethyl acetate are in the range of 1116 μg/mL, and this activity is explained in terms of a synergic effect generated by SQL different to LTC. The IC50 values of extracts incorporated into polymer micelles formed by Pluronic F127 are 200 times lower than those measured for ethyl acetate extract applied in homogeneous solution. Finally, by assessing changes in cell and nuclear morphology it is suggested that the observed cytotoxicity of free and entrapped extracts is produced by apoptotic process. In conclusion, these results suggest that plant extracts may show an increased activity as result of synergic effect of minority components, and an important enhancement of cytotoxicity is induced by entrapment into polymer micelles.

References

  1. J. Alonso-Castro, M. L. Villarreal, L. A. Salazar-Olivo, M. Gomez-Sanchez, F. Dominguez, A. Garcia-Carranca. J. Ethnopharmacol. 133, 945 (2011).
  2. J. L. Hartwell. Plants Used Against Cancer: A Survey. Quarterman, Lawrence, MA, USA (1982).
  3. G. M. Cragg, P. G. Grothaus, D. J. Newman. Chem. Rev. 109, 3012 (2009).
  4. M. Tascilar, F. A. De Jong, J. Verweij, R. S. Mathijssen. Oncologist. 11, 732 (2006).
  5. Van Waes. Clin. Cancer Res. 13, 1076 (2007).
  6. Van Waes, M. Yu, L. Nottingham, M. Karin. Clin. Cancer Res. 13, 4956 (2007).
  7. A. S. Baldwin. J. Clin. Inv. 107, 241 (2001).
  8. Basseres, A. Baldwin. Oncogene. 25, 6817 (2006).
  9. A. Loercher, T. L. Lee, J. L. Ricker, A. Howard, J. Geoghegen, Z. Chen, J. B. Sunwoo, R. Sitcheran, E. Y. Chuang, J. B. Mitchell, A. S. Baldwin, C. Van Waes. Cancer Res. 64, 6511 (2004).
  10. J. Wang, H. An, M. W. Mayo, A. S. Baldwin, W. G. Yarbrough. Cancer Cell. 12, 239 (2007).
  11. S. P. Hehner, T. G. Hofmann, W. Droge, M. L. Schmitz. J. Immunol. 163, 5617 (1999).
  12. T. H. Koo, J. H. Lee, Y. J. Park, Y. S. Hong, H. S. Kim, K. W. Kim, J. J. Lee. Planta Med. 67, 103 (2001).
  13. M. T. Lindenmeyer, A. Hrenn, C. Kern, V. Castro, R. Murillo, S. Muller, S. Laufer, J. Schulte-Monting, B. Siedle, I. Merfort. Bioorganic Med. Chem. 14, 2487 (2006).
  14. P. Rungeler, V. Castro, G. Mora, N. Goren, W. Vichnewski, H. L. Pahl, I. Merfort, T. J. Schmidt. Bioorganic Med. Chem. 7, 2343 (1999).
  15. K.-Y. Lee, E.-S. Huang, C. Piantadosi, J. S. Pagano, T. A. Geissman. Cancer Res. 31, 1649 (1971).
  16. P. Bremner, D. Rivera, M. A. Calzado, C. Obon, C. Inocencio, C. Beckwith, B. L. Fiebich, E. Munoz, M. Heinrich. J. Ethnopharmacol. 124, 295 (2009).
  17. M. L. Guzman, L. Karnischky, X. J. Li, S. J. Neering, R. M. Rossi, C. T. Jordan. Blood. 104, 697A (2004).
  18. M. L. Guzman, C. T. Jordan. Expert Opinion on Biological Therapy. 5, 1147 (2005).
  19. J. Sweeney, S. Mehrotra, M. R. Sadaria, S. Kumar, N. H. Shortle, Y. Roman, C. Sheridan, R. A. Campbell, D. J. Murry, S. Badve, H. Nakshatri. Mol Cancer Ther. 4, 1004 (2005).
  20. L. J. Zhao, Y. H. Xu, Y. Li. J. Dig. Dis. 10, 172 (2009).
  21. Oka, K. Nishimura, M. Shiba, Y. Nakai, Y. Arai, M. Nakayama, H. Takayama, H. Inoue, A. Okuyama, N. Nonomura. Int. J. Cancer. 120, 2576 (2007).
  22. J. Y. Cho, A. R. Kim, J. H. Jung, T. Chun, M. H. Rhee, E. S. Yoo. Eur. J. Pharmacol. 492, 85 (2004).
  23. R. Martinez, B. Ayamante, J. A. Nunez-Alarcon, A. R. de Vivar. Phytochem. 18, 1527 (1979).
  24. R. Martinez, V. Kesternich, E. Gutierrez, H. Dolz, H. Mansilla. Planta Med. 61, 188 (1995).
  25. Bosio, G. Tomasoni, R. Martinez, A. F. Olea, H. Carrasco, J. Villena. Chem. Biol. Inter. 242, 415 (2015).
  26. S. P. Hehner, M. Heinrich, P. M. Bork, M. Vogt, F. Ratter, V. Lehmann, K.Schulze-Osthoff, W. Droge, M. L. Schmitz. J. Biol. Chem. 273, 1288 (1998).
  27. C. Wu, F. Chen, J. W. Rushing, X. Wang, H. J. Kim, G. Huang, V. Haley-Zitlin, G. He. J. Med. Food. 9, 55 (2006).
  28. P. M. Bork, M. L. Schmitz, M. Kuhnt, C. Escher, M. Heinrich. FEBS Letters. 402, 85 (1997).
  29. Y. T. Tanaka, K. Tanaka, H. Kojima, T. Hamada, T. Masutani, M. Tsuboi, Y. Akao. Bioorg. Med. Chem. Lett. 23, 518 (2013).
  30. S. Nasim, P. A. Crooks. Bioorg. Med. Chem. Lett. 18, 3870 (2008).
  31. S. Neelakantan, S. Nasim, M. L. Guzman, C. T. Jordan, P. A. Crooks. Bioorg. Med. Chem. Lett. 19, 4346 (2009).
  32. K. Kataoka, A. Harada, Y. Nagasaki. Adv. Drug Deliv. Rev. 47, 113 (2001).
  33. N. Rapoport. Prog. Polym. Sci. 32, 962 (2007).
  34. Y. Lu, K. Park. Int. J. Pharm. 453, 198 (2013).
  35. Y. Matsumura, K. Kataoka. Cancer Sci. 100, 572 (2009).
  36. R. Nagarajan. Colloids Surf., B. 16, 55 (1999).
  37. P. Alexandridis, T. A. Hatton. Colloids Surf., A. 96, 1 (1995).
  38. V. Kabanov, E. V. Batrakova, V. Y. Alakhov. J. Control. Release. 82, 189 (2002).
  39. R. Basak, R. Bandyopadhyay. Langmuir. 29, 4350 (2013).
  40. M. A. James-Smith, D. Shekhawat, B. M. Moudgil, D. O. Shah. Langmuir. 23, 1640 (2007).
  41. M. Y. Kozlov, N. S. Melik-Nubarov, E. V. Batrakova, A. V. Kabanov. Macromolecules. 33, 3305 (2000).
  42. F. Olea, H. Carrasco, L. Espinoza, B. Acevedo. J.Chil.Chem.Soc. 59, 2451 (2014).
  43. T. Miller, G. van Colen, B. Sander, M. M. Golas, S. Uezguen, M. Weigandt, A. Goepferich. Pharm. Res. 30, 584 (2013).
  44. V. Vichai, K. Kirtikara. Nat. Protoc. 1, 1112 (2006).
  45. P. D. Allen, A. C. Newland. Apoptosis detection by DNA analysis, in Molecular Diagnosis of Cancer, F.E. Cotter, 16. Humana Press, New Jersey (1996).
  46. M. Suffness, J. M. Pezzuto. Assays related to cancer drug discovery, in Methods in Plant Biochemistry: Assays for Bioactivity, K. Hosttetmann. Academic Press, London (1990).
  47. B. Acevedo, F. Martinez, A. Olea. J. Chil. Chem.Soc. 58, 2038 (2013).

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