Jasmonates in cancer therapy

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Jasmonates in cancer therapy.

E Flescher

Cancer Lett, January 8, 2007; 245(1-2): 1-10.

Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv

University, Ramat Aviv, 69978, Tel Aviv Israel.

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.

PMID: 16600475