Brazilian scientist is part of elite group of researchers fighting cancer, obtains an unprecedented patent in the United States.

Abstract

In 1966, researchers at Princeton University in the United States first isolated a family of vegetable stress hormones called Jasmonates, a family with several elements with structures similar to the human prostaglandin, that had stress-reducing properties. These hormones developed over millions of years as plants adapted to nature’s threats including hydration stress or attacks by predators. Similar to animals, plants are faced with many of the same problems – a need for regulation of the metabolic process, healthy reproduction and for the defense against enemies. Jasmonates within plants serve a key role in the genes as well as in the metabolic regulation. They are also responsible for a plant’s defense, the response for trauma, reproduction and possibly vital to their own communication (Liechti and Farmer, 2002). Plants’ stress hormones are known as the key activators in cellular response, including cell death and diverse stress situations in plants.Dr. Eliezer Flescher of Tel Aviv University theorized that the jasmonate cellular response function might be something to test for in human cells, more specifically cancer cells. Dr. Flescher through trial and error isolated a member of the Jasmonate family, the methyl jasmonate (“MJ”), as an agent that could have cancer-fighting capabilities. Dr. Flescher observed that the methyl jasmonate suppressed the proliferation of lymphoblastic leukemia cells and caused suppression of the cell proliferation in the other humans’ cancer cells including prostate, breast and melanoma (Fingrut and Flescher, 2002).Dr. Eliezer Flescher’s studies concluded that methyl jasmonate, could induce direct perturbation of cancer cells mitochondria leading to release of the cytochrome c and eventual cell death. However, the most important characteristic of the methyl jasmonate was its ability to selective kill cancer cells while sparing normal cell activity. Dr Flescher’s tests were performed within a mixed population of normal and leukemic cells derived from blood of chronic lymphocytic leukemia (CLL) patients. Methyl jasmonate killed preferentially only the leukemia cells (Flescher, 2005). Methyl jasmonate thus became an ideal candidate to initiate apoptosis, or programmed cell death in cancerous cells. At first, the explanation for the mechanism of action of the jasmonate killing the cancer cells stemmed back to the early 1920s when the most striking biochemical phenotype of cancer, its aberrant energy metabolism, was discovered. Unlike normal tissue cells that derive much of their energy (ATP) by metabolizing sugar glucose into carbon dioxide and water in a process that involves oxygen-dependent organelles called mitochondria, studies performed by Otto Warburg showed that cancer cells frequently relied less on mitochondria by obtaining as much as 50% of their ATPs by metabolizing glucose directly into lactic acid, even in the presence of oxygen. This phenotype became known as the Warburg Effect (Pedersen, 2007).Mitochondria in cancer cells generally have a malfunction of their selective permeability (Flescher, 2005). Most of the studies using jasmonates to treat cancer cells were taking advantage of a defect in the mitochondria in those cells, as the selective action of methyl jasmonate can safely be used to initiate apoptosis in defective cells while leaving healthy cells untouched. Flescher and his group found out three possible pathways to better describe how jasmonates selectively targeted cancer cells: 1 – the bio-energetic mechanism-jasmonate induced severe ATP depletion in cancer cells via mitochondrial perturbation, 2 – the re-differentiation mechanism-jasmonate induced re-differentiation in human myeloid leukemia cells via mitogen- activated protein kinase (MAPK) activity. 3- The reactive oxygen species (ROS)-mediated mechanism -jasmonate induced apoptosis in lung carcinoma cells via the generation of hydrogen peroxide, and pro-apoptotic protein of the Bcl-2 family. Many similarities between the effects of jasmonates on plants 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 (Flescher, 2007).Studies intensified as others international groups began researching plant stress hormones as promising approaches and possible therapies for cancer treatments. Many studies used pure methyl jasmonate or a similar cis-formulation of MJ as others elements from this plant hormone’s family. The Methyl Jasmonate is a chemically fragile ester structure, it is not easily delivered to the cancerous cells, usually degrading before it reaches the tumor. Among