AKR1C isoforms represent a novel cellular target for jasmonates alongside their mitochondrial-mediated effects

Related Experiment Video

Updated: Jun 22, 2026

Optimized Automated Analysis of Live Neuronal Mitochondria Homeostasis Modulation by Isoform-Specific Retinoic Acid Receptors
08:33

Optimized Automated Analysis of Live Neuronal Mitochondria Homeostasis Modulation by Isoform-Specific Retinoic Acid Receptors

Published on: July 28, 2023

Nicholas J Davies1, Rachel E Hayden, Paul J Simpson

  • 1College of Life and Environmental Sciences, School of Biosciences, University of Birmingham, Birmingham, United Kingdom.

Cancer Research
|June 3, 2009
PubMed

Insights

Jasmonates, including jasmonic acid (JA) and methyl jasmonate (MeJ), inhibit aldo-keto reductase (AKR1C) enzymes crucial in cancer. Methyl jasmonate shows greater potency in cells, potentially offering new cancer treatment strategies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Aldo-keto reductase (AKR) superfamily enzymes, particularly AKR1C subfamily, are implicated in cancer progression.
  • Jasmonates, plant stress hormones structurally similar to prostaglandins, exhibit anticancer properties.
  • Novel therapeutic strategies targeting AKR1C enzymes are needed for cancer chemoprevention and treatment.

Purpose of the Study:

  • To investigate the inhibitory effects of jasmonic acid (JA) and methyl jasmonate (MeJ) on human AKR1C isoforms.
  • To explore the mechanisms underlying the anticancer activities of jasmonates in cancer cells.
  • To identify AKR1C isoforms as novel molecular targets for jasmonate-based cancer therapies.

Main Methods:

  • Enzyme inhibition assays using recombinant human AKR1C isoforms.
  • Cellular assays to assess jasmonate potency, cellular uptake, and reactive oxygen species (ROS) generation.
  • Mitochondrial superoxide (MSO) detection and correlation with cellularity in acute myelogenous leukemia cell lines (HL-60 and KG1a).

Main Results:

  • Both JA and MeJ inhibited all four human AKR1C isoforms.
  • MeJ demonstrated greater potency in cellular systems compared to JA, attributed to enhanced cellular uptake.
  • MeJ induced significant mitochondrial superoxide (MSO) levels and showed a correlation between MSO formation and reduced cellularity in leukemia cell lines.

Conclusions:

  • AKR1C isoforms represent a novel therapeutic target for jasmonates in cancer treatment.
  • Jasmonates, particularly MeJ, show promise as adjunctive therapies for malignancies due to their ability to inhibit AKR1C enzymes and induce cancer cell death.
  • Further research into jasmonate derivatives may yield effective chemopreventive or therapeutic agents for various cancers.

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