Microbial Biotechnology
  Molecular Biology and Genetics
Electronic Journal of Biotechnology ISSN: 0717-3458 Vol. 14 No. 2, Issue of March 15, 2011
© 2011 by Pontificia Universidad Católica de Valparaíso -- Chile Received October 26, 2010 / Accepted January 28, 2011
DOI: 10.2225/vol14-issue2-fulltext-11  

New stereoisomeric derivatives of jasmonic acid generated by biotransformation with the fungus Gibberella fujikuroi affect the viability of human cancer cells

Marcela Carvajal*1 · Luis Espinoza1 · Silvia Caggia2 · Venera Cardile2 · Juan A. Garbarino1 · Hugo Peña-Cortés3 · Alessandra Russo4

1Laboratorio de Química de Productos Naturales y Síntesis Orgánica, Departamento de Química, Universidad Técnica Federico Santa María, Valparaíso, Chile
2Department of Physiological Sciences, University of Catania, Catania, Italy
3Centro de Biotecnología “D. Alkalay L.”, Universidad Técnica Federico Santa María, Valparaíso, Chile
4Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, Catania, Italy

*Corresponding author: marcela.carvajal@usm.cl

Keywords: apoptosis, biotransformations, cancer cells, cell vitality, Gibberella fujikuroi, jasmonic acid.

Abstract   Full Text

Background: Several studies have shown that (-)-Jasmonic acid, (+)-7-iso-Jasmonic acid and its methyl ester, methyl jasmonate, have anti-cancer activity in vitro and in vivo, exhibiting selective cytotoxicity towards cancer cells. The degree of activity of these molecules is strongly related to their stereochemistry. The biotransformation of known compounds, natural or synthesized, related to interesting biological activities, generates new molecules displaying new improved properties compared with the original ones, increasing its value and providing new more effective products. Therefore, based on the above rationales and observations, in this work a biotransformation protocol to modify the chemical structure of the plant hormone jasmonic acid by using the fungus Gibberella fujikuroi was established.
Results: The three jasmonic acid derivatives obtained, 3(S)-Hydroxy-2(R)-(2Z-butenyl)-cyclopentane-1(R)-acetic acid(1), 3(R)-Hydroxy-2(R)-(2Z-butenyl)-cyclopentane-1(R)-acetic acid (2), 3-Hydroxy-2(S)-(2Z-butenyl)-cyclopentane-1(S)-acetic acid (3), were tested for cell-growth inhibition activity towards the human cancer epithelial cell line, the oral squamous carcinoma cells (KB). The results obtained show that jasmonic acid derivatives (1-3) are active on human cancer cells examined in different concentration ranges, with IC50 value less than of 25 µM. The compound 3, with the same molecular structure of compounds 1 and 2, but with different stereochemistry, was more active confirming that the activity of jasmonate compounds is related to their stereochemistry and to substituents in the cyclopentane ring. In this study, we also tested the potential proapoptotic activity of compound 3, and our data suggest that it, as other jasmonate compounds, is able to trigger apoptotic death in cancer cells. This event may be correlated at an elevation of reactive oxygen species (ROS). Administration of N-acetylcysteine (NAC) prevented compound 3 cytotoxicity.
Conclusions: This work shows for the by first time the production of hydroxylated derivatives of JA by biotransformation. The activity observed of these compounds in cancer cells is higher than the observed with JA and is strongly related to its stereochemistry.

Supported by UNESCO / MIRCEN network