Microbial Biotechnology |
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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 |
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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.
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.
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