Jasmonates in cancer therapy.
Several groups have reported in recent years that members of the plant stress hormones family of jasmonates, and some of their synthetic derivatives, exhibit anti-cancer activity in vitro and in vivo. Jasmonates increased the life span of EL-4 lymphoma-bearing mice, and exhibited selective cytotoxicity towards cancer cells while sparing normal blood lymphocytes, even when the latter were part of a mixed population of leukemic and normal cells drawn from the blood of chronic lymphocytic leukemia (CLL) patients. Jasmonates join a growing number of old and new cancer chemotherapeutic compounds of plant origin. Three mechanisms of action have been proposed to explain the anti-cancer activity of jasmonates. These include: (1) The bio-energetic mechanism-jasmonates induce severe ATP depletion in cancer cells via mitochondrial perturbation; (2) The re-differentiation mechanism-jasmonates induce re-differentiation in human myeloid leukemia cells via mitogen-activated protein kinase (MAPK) activity; (3) The reactive oxygen species (ROS)-mediated mechanism-jasmonates induce apoptosis in lung carcinoma cells via the generation of hydrogen peroxide, and pro-apoptotic proteins of the Bcl-2 family. Several similarities between the effects of jasmonates on plant and cancer cells have been recorded, suggesting that additional analysis of jasmonate effects in plant cells may contribute to a deeper understanding of the anti-cancer actions of these compounds. Those similarities include: induction of cell death, suppression of proliferation and cell cycle arrest, MAPK induction, ROS generation, and enhancement of heat-shock proteins (HSP) expression. Finally, jasmonates can induce death in drug-resistant cells. The drug resistance was conferred by either p53 mutation or P-glycoprotein (P-gp) over-expression. In summary, the jasmonate family of novel anti-cancer agents presents new hope for the development of cancer therapeutics, which should attract further scientific and pharmaceutical interest.
Flescher
Eliezer
E
Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 69978, Tel Aviv Israel. flascher@post.tau.ac.il
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003517:Cyclopentanes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D054883:Oxylipins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D003517:Cyclopentanes; D054883:Oxylipins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C011006:jasmonic acid; D020928:Mitogen-Activated Protein Kinases