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

Abstract

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 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.

Characterisation of the antiproliferative constituents and activity of Ficus exasperata (Vahl) on ovarian cancer cells –a preliminary investigation

“…The principle applied involves the ability of metabolically active cells being able to convert the dye to water-insoluble dark blue formazan and in the process reducing cleavage of the tetrazolium ring [13]. MTT was dissolved in Phosphate Buffer Solution to produce a 5 mg/mL solution; it was then filtered using Millex Syringe Driven Filter Unit (0.22 μm) before being combined with media to produce 10 mL MTT-media solution (20% MTT : 80% media).…”

A Review (Research and Patents) on Jasmonic Acid and Its Derivatives

“…The apoptosis evocated by this new molecule appeared, at least in part, to be associated with an increase in reactive oxygen species (ROS) production . A study indicated that three JA derivatives obtained by biotransformation were specifically active on several types of cancer cells . One of the α‐haloenone analogs, methyl 5‐chloro‐4,5‐didehydrojasmonate or J7, a methyl jasmonate (MeJA) analog, induced significant apoptosis by activation of caspase‐3 and the mitochondrial apoptosis signaling pathway in Hep3B cells .…”

Defense Induced by Jasmonic Acid: A Review

“…The apoptosis evocated by this new molecule appeared to associated with an increase in reactive oxygen species (ROS) production (Reinbothe et al, 2009). A study indicated that three JA derivatives obtained by biotransformation were specifically active on several types of cancer cells (Carvajal et al, 2011(Carvajal et al, , 2012(Carvajal et al, , 2013.…”