Jasmonates--a new family of anti-cancer agents.

Since salicylate, a plant stress hormone, suppresses the growth of various types of cancer cells, it was deemed of interest to investigate whether the jasmonate family of plant stress hormones is endowed with anti-cancer activities. Cell lines representing a wide spectrum of malignancies, including prostate, breast and lung, exhibit sensitivity to the cytotoxic effects of methyl jasmonate (MJ). Jasmonates induced death in leukemic cells isolated from the blood of chronic lymphocytic leukemia (CLL) patients and increased significantly the survival of lymphoma-bearing mice. Among the naturally occurring jasmonates, MJ is the most active, while the synthetic methyl-4,5-didehydrojasmonate, was approximately 29-fold more active than MJ. The cytotoxic activity of MJ is independent of transcription and translation. Studies have suggested several mechanisms of action. It appears that while prolonged exposures to relatively low concentrations of jasmonates induce growth arrest and re-differentiation in myeloid leukemia cells, higher concentrations of MJ induce direct perturbation of cancer cell mitochondria, leading to the release of cytochrome c and eventual cell death. A most important characteristic of jasmonates is their ability to selectively kill cancer cells while sparing normal cells. Even within a mixed population of normal and leukemic cells derived from the blood of CLL patients, MJ killed preferentially the leukemic cells. In conclusion, jasmonates present a unique class of anti-cancer compounds which deserves continued research at the basic and pharmaceutical levels in order to yield novel chemotherapeutic agents against a range of neoplastic diseases.