Methyl jasmonate: a plant stress hormone as an anti-cancer drug.
Jasmonates act as signal transduction intermediates when plants are subjected to environmental stresses such as UV radiation, osmotic shock and heat. In the past few years several groups have reported that jasmonates exhibit anti-cancer activity in vitro and in vivo and induce growth inhibition in cancer cells, while leaving the non-transformed cells intact. Recently, jasmonates were also discovered to have cytotoxic effects towards metastatic melanoma both in vitro and in vivo. Three mechanisms of action have been proposed to explain this anti-cancer activity. The bio-energetic mechanism - jasmonates induce severe ATP depletion in cancer cells via mitochondrial perturbation. Furthermore, methyl jasmonate (MJ) has the ability to detach hexokinase from the mitochondria. Second, jasmonates induce re-differentiation in human myeloid leukemia cells via mitogen-activated protein kinase (MAPK) activity and were found to act similar to the cytokinin isopentenyladenine (IPA). Third, jasmonates induce apoptosis in lung carcinoma cells via the generation of hydrogen peroxide, and pro-apoptotic proteins of the Bcl-2 family. Combination of MJ with the glycolysis inhibitor 2-deoxy-d-glucose (2DG) and with four conventional chemotherapeutic drugs resulted in super-additive cytotoxic effects on several types of cancer cells. Finally, jasmonates have the ability to induce death in spite of drug-resistance conferred by either p53 mutation or P-glycoprotein (P-gp) over-expression. In summary, the jasmonates are anti-cancer agents that exhibit selective cytotoxicity towards cancer cells, and thus present hope for the development of cancer therapeutics.
Cohen
Sharon
S
Department of Clinical Microbiology and Immunology, Sacker Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Flescher
Eliezer
E
D000085:Acetates / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003517:Cyclopentanes / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy; D054883:Oxylipins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D010937:Plant Growth Regulators / Q000494:pharmacology
D000085:Acetates; D000970:Antineoplastic Agents; D003517:Cyclopentanes; D054883:Oxylipins; D010937:Plant Growth Regulators; C072239:methyl jasmonate