Induction of differentiation of human myeloid leukemia cells by jasmonates, plant hormones

Ishii, Yuki; Kiyota, Hiromasa; Sakai, Shingo; Honma, Yoshio

doi:10.1038/sj.leu.2403421

Cited by 56 publications

(63 citation statements)

References 29 publications

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“…Of particular interest here is the potential of jasmonates or derivatives thereof in hematolymphoid malignancy. The earliest reports of jasmonate activities included suppressed proliferation and induced apoptosis of AML, lymphoblastic leukemia, and lymphoma cell lines (25,43,44). This activity was shown to be selective because normal peripheral blood lymphocytes were spared even in mixed populations with chronic lymphocytic leukemia cells (29).…”

Section: Discussionmentioning

confidence: 99%

“…It therefore remains to be determined whether the MSO generation reported here is a direct effect of MeJ or is an epiphenomenon of mitochondrial damage. Furthermore, Ishii and colleagues (43) previously showed that MeJ-promoted HL-60 cell differentiation was associated with increased mitogen-activated protein kinase (MAPK) activity. Treatment of HL-60 cells with the MAPK inhibitor PD98059 both diminished this activation and the differentiation seen in response to MeJ.…”

Section: Discussionmentioning

confidence: 99%

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AKR1C Isoforms Represent a Novel Cellular Target for Jasmonates alongside Their Mitochondrial-Mediated Effects

et al. 2009

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Members of the aldo-keto reductase (AKR) superfamily, particularly the AKR1C subfamily, are emerging as important mediators of the pathology of cancer. Agents that inhibit these enzymes may provide novel agents for either the chemoprevention or treatment of diverse malignancies. Recently, jasmonates, a family of plant stress hormones that bear a structural resemblance to prostaglandins, have been shown to elicit anticancer activities both in vitro and in vivo. In this study, we show that jasmonic acid (JA) and methyl jasmonate (MeJ) are capable of inhibiting all four human AKR1C isoforms. Although JA is the more potent inhibitor of recombinant AKR1C proteins, including the in vitro prostaglandin F synthase activity of AKR1C3, MeJ displayed greater potency in cellular systems that was, at least in part, due to increased cellular uptake of MeJ. Moreover, using the acute myelogenous leukemia cell lines HL-60 and KG1a, we found that although both jasmonates were able to induce high levels of reactive oxygen species in a dose-dependent fashion, only MeJ was able to induce high levels of mitochondrial superoxide (MSO), possibly as an epiphenomenon of mitochondrial damage. There was a strong correlation observed between MSO formation at 24 hours and reduced cellularity at day 5. In conclusion, we have identified AKR1C isoforms as a novel target of jasmonates in cancer cells and provide further evidence of the promise of these compounds, or derivatives thereof, as adjunctive therapies in the treatment of cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

AKR1C Isoforms Represent a Novel Cellular Target for Jasmonates alongside Their Mitochondrial-Mediated Effects

et al. 2009

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“…Plant stress hormones of the jasmonate family, small hydrophobic molecules, have been previously shown to be endowed with anticancer capabilities (Fingrut and Flescher, 2002;Ishii et al, 2004), allowing for the prolonged survival of tumor-bearing animals (Fingrut and Flescher, 2002;Heyfets and Flescher, 2007) and suppression of the metastasis of murine melanoma . Indeed, jasmonates are selectively toxic toward cancer cells (Fingrut and Flescher, 2002;Rotem et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Methyl jasmonate binds to and detaches mitochondria-bound hexokinase

et al. 2008

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“…Likewise, it is reported the synthesis of numerous and varied series of derivatives of MeJA, predominantly halogenated (-Cl,-Br, -F) structures, which similar to JA and its derivatives, they exhibit interesting and in some cases potent anti-neoplastic properties (Ishii et al 2004;Reischer et al 2007;Park et al 2010;Zhao et al 2010), but it is noteworthy that in each of the proposed series does not have reported the production of derivatives with keto group reduced and the potential inhibition of cell growth observed with these series of compounds does not exceed the IC50 obtained with the derivatives reported here. Qian et al 2004 reported that synthetic hydroxyl-containing jasmonates may induce different levels of plant defense responses, which are associated with different levels of enhanced metabolic activity for secondary metabolite biosynthesis.…”

Section: Study On Tumor Cell Linesmentioning

confidence: 99%

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

Carvajal¹,

Espinoza²,

Caggia³

et al. 2011

Electro Journal of Biotech

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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.

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Induction of differentiation of human myeloid leukemia cells by jasmonates, plant hormones

Cited by 56 publications

References 29 publications

AKR1C Isoforms Represent a Novel Cellular Target for Jasmonates alongside Their Mitochondrial-Mediated Effects

AKR1C Isoforms Represent a Novel Cellular Target for Jasmonates alongside Their Mitochondrial-Mediated Effects

Methyl jasmonate binds to and detaches mitochondria-bound hexokinase

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

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