Jasmonates: Plant Stress Hormones as Anticancer Agents

Jasmonates are a group of plant stress hormones which are among the most potent regulators of defense-related mechanisms in plants. In recent years, several groups have reported that jasmonates are endowed with anti-cancer activities both in vitro and in vivo. Jasmonates were shown to induce death and inhibit the proliferation and the migration of various cancer cell types, including drug-resistant cells. Moreover, jasmonates were shown to impair the angiogenic process, which is essential for tumor progression. In line with their anti-cancer activities in vitro, jasmonates were shown to increase the survival of lymphoma-bearing mice and to inhibit the development of lung metastases in a mouse melanoma model. Importantly, jasmonates are highly selective towards cancer cells and have little or no effect on normal cells, creating a wide therapeutic window. Recently, a first-in-man study demonstrated that methyl jasmonate has a beneficial effect in treating human pre-cancerous and cancerous skin lesions. Several mechanisms were shown to mediate the anti-cancer activities of jasmonates. These include: direct perturbation of mitochondria, production of reactive oxygen species, induction of cellular differentiation, inhibition of aldo-keto reductases, upregulation of several pro-apoptotic proteins and downregulation of anti-apoptotic proteins. A number of research groups have taken the natural jasmonate compounds as a starting point to prepare and evaluate a wide variety of synthetic jasmonate derivatives. Several of these derivatives exhibited enhanced anti-cancer activities in vitro and in vivo. While the vast majority of studies on jasmonates as potential drugs have been performed in the cancer arena, these compounds have also been evaluated as anti-parasitic and anti-inflammatory agents. In conclusion, jasmonates present a unique class of anti-cancer compounds which deserves continued research at the basic, pharmaceutical and clinical levels in order to yield novel chemotherapeutic agents against a range of neoplastic diseases.