New stereoisomeric derivatives of jasmonic acid generated by biotransformation with the fungus Gibberella fujikuroi affect the viability of human cancer cells
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 thei...
Guardado en:
| Autores principales: | , , , , , , |
|---|---|
| Lenguaje: | English |
| Publicado: |
Pontificia Universidad Católica de Valparaíso
2011
|
| Materias: | |
| Acceso en línea: | http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-34582011000200007 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:scielo:S0717-34582011000200007 |
|---|---|
| record_format |
dspace |
| spelling |
oai:scielo:S0717-345820110002000072011-05-26New stereoisomeric derivatives of jasmonic acid generated by biotransformation with the fungus Gibberella fujikuroi affect the viability of human cancer cellsCarvajal,MarcelaEspinoza,LuisCaggia,SilviaCardile,VeneraGarbarino,Juan APeña-Cortés,HugoRusso,Alessandra 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-pentenyl)-cyclopentane-1(R)-acetic acid (1), 3(R)-Hydroxy-2(R)-(2Z-pentenyl)-cyclopentane-1(R)-acetic acid (2), 3-Hydroxy-2(S)-(2Z-pentenyl)-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 �M. 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.info:eu-repo/semantics/openAccessPontificia Universidad Católica de ValparaísoElectronic Journal of Biotechnology v.14 n.2 20112011-03-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-34582011000200007en |
| institution |
Scielo Chile |
| collection |
Scielo Chile |
| language |
English |
| topic |
apoptosis biotransformations cancer cells cell vitality Gibberella fujikuroi jasmonic acid |
| spellingShingle |
apoptosis biotransformations cancer cells cell vitality Gibberella fujikuroi jasmonic acid Carvajal,Marcela Espinoza,Luis Caggia,Silvia Cardile,Venera Garbarino,Juan A Peña-Cortés,Hugo Russo,Alessandra New stereoisomeric derivatives of jasmonic acid generated by biotransformation with the fungus Gibberella fujikuroi affect the viability of human cancer cells |
| description |
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-pentenyl)-cyclopentane-1(R)-acetic acid (1), 3(R)-Hydroxy-2(R)-(2Z-pentenyl)-cyclopentane-1(R)-acetic acid (2), 3-Hydroxy-2(S)-(2Z-pentenyl)-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 �M. 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. |
| author |
Carvajal,Marcela Espinoza,Luis Caggia,Silvia Cardile,Venera Garbarino,Juan A Peña-Cortés,Hugo Russo,Alessandra |
| author_facet |
Carvajal,Marcela Espinoza,Luis Caggia,Silvia Cardile,Venera Garbarino,Juan A Peña-Cortés,Hugo Russo,Alessandra |
| author_sort |
Carvajal,Marcela |
| title |
New stereoisomeric derivatives of jasmonic acid generated by biotransformation with the fungus Gibberella fujikuroi affect the viability of human cancer cells |
| title_short |
New stereoisomeric derivatives of jasmonic acid generated by biotransformation with the fungus Gibberella fujikuroi affect the viability of human cancer cells |
| title_full |
New stereoisomeric derivatives of jasmonic acid generated by biotransformation with the fungus Gibberella fujikuroi affect the viability of human cancer cells |
| title_fullStr |
New stereoisomeric derivatives of jasmonic acid generated by biotransformation with the fungus Gibberella fujikuroi affect the viability of human cancer cells |
| title_full_unstemmed |
New stereoisomeric derivatives of jasmonic acid generated by biotransformation with the fungus Gibberella fujikuroi affect the viability of human cancer cells |
| title_sort |
new stereoisomeric derivatives of jasmonic acid generated by biotransformation with the fungus gibberella fujikuroi affect the viability of human cancer cells |
| publisher |
Pontificia Universidad Católica de Valparaíso |
| publishDate |
2011 |
| url |
http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-34582011000200007 |
| work_keys_str_mv |
AT carvajalmarcela newstereoisomericderivativesofjasmonicacidgeneratedbybiotransformationwiththefungusgibberellafujikuroiaffecttheviabilityofhumancancercells AT espinozaluis newstereoisomericderivativesofjasmonicacidgeneratedbybiotransformationwiththefungusgibberellafujikuroiaffecttheviabilityofhumancancercells AT caggiasilvia newstereoisomericderivativesofjasmonicacidgeneratedbybiotransformationwiththefungusgibberellafujikuroiaffecttheviabilityofhumancancercells AT cardilevenera newstereoisomericderivativesofjasmonicacidgeneratedbybiotransformationwiththefungusgibberellafujikuroiaffecttheviabilityofhumancancercells AT garbarinojuana newstereoisomericderivativesofjasmonicacidgeneratedbybiotransformationwiththefungusgibberellafujikuroiaffecttheviabilityofhumancancercells AT penacorteshugo newstereoisomericderivativesofjasmonicacidgeneratedbybiotransformationwiththefungusgibberellafujikuroiaffecttheviabilityofhumancancercells AT russoalessandra newstereoisomericderivativesofjasmonicacidgeneratedbybiotransformationwiththefungusgibberellafujikuroiaffecttheviabilityofhumancancercells |
| _version_ |
1718441834756177920 |