Methyl Jasmonate: Putative Mechanisms of Action on Cancer Cells Cycle, Metabolism, and Apoptosis

Abstract

Methyl jasmonate (MJ), an oxylipid that induces defense-related mechanisms in plants, has been shown to be active against cancer cells both in vitro and in vivo, without affecting normal cells. Here we review most of the described MJ activities in an attempt to get an integrated view and better understanding of its multifaceted modes of action. MJ (1) arrests cell cycle, inhibiting cell growth and proliferation, (2) causes cell death through the intrinsic/extrinsic proapoptotic, p53-independent apoptotic, and nonapoptotic (necrosis) pathways, (3) detaches hexokinase from the voltage-dependent anion channel, dissociating glycolytic and mitochondrial functions, decreasing the mitochondrial membrane potential, favoring cytochrome c release and ATP depletion, activating pro-apoptotic, and inactivating antiapoptotic proteins, (4) induces reactive oxygen species mediated responses, (5) stimulates MAPK-stress signaling and redifferentiation in leukemia cells, (6) inhibits overexpressed proinflammatory enzymes in cancer cells such as aldo-keto reductase 1 and 5-lipoxygenase, and (7) inhibits cell migration and shows antiangiogenic and antimetastatic activities. Finally, MJ may act as a chemosensitizer to some chemotherapics helping to overcome drug resistant. The complete lack of toxicity to normal cells and the rapidity by which MJ causes damage to cancer cells turn MJ into a promising anticancer agent that can be used alone or in combination with other agents.

A Novel Peroxisome Proliferator-activated Receptor (PPAR)γ Agonist 2-Hydroxyethyl 5-chloro-4,5-didehydrojasmonate Exerts Anti-Inflammatory Effects in Colitis

“…Methyl jasmonate is a member of the plant stress hormone family of jasmonates, the most potent regulator of defense-related mechanisms in plants (6). Because of similar partial structure to anti-inflammatory cyclopentenone prostaglandins, methyl jasmonate was selected as the starting material for the synthesis of a series of enone fatty acid-based anti-inflammatory compounds (7).…”

Methyl jasmonate and its potential in cancer therapy

“…7 In view of its roles in the induction of suicide programs in cancer cell lines, and of its potential and promise as an anticancer drug, great efforts have been made to explore the molecular mechanisms of MeJa action(s) on cancer cells and mitochondria. [7][8][9][10] However, it still remains unclear why apoptosis programs are specifically activated by MeJa in cancer cells, but not in normal human cells. Even so, it has been overwhelmingly proposed that MeJa is a novel class of anticancer drugs that act directly and selectively against tumor cells both in vitro and in vivo, without affecting normal cells such as lymphocytes.…”

“…Even so, it has been overwhelmingly proposed that MeJa is a novel class of anticancer drugs that act directly and selectively against tumor cells both in vitro and in vivo, without affecting normal cells such as lymphocytes. [7][8][9][10] Although the susceptibility of cancer cells and mitochondria to MeJa was shown to be dependent on the evaluated expression of hexokinase, 10 a key hallmark of many types of cancer cells, the mechanisms underlying MeJa-induced detachment of hexokinase from mitochondria and subsequent apoptosis is yet to be known. Hexokinase II is the major form of hexokinase in cancer cells, however MeJa shows no specificity and selectivity in binding hexokinase I and hexokinase II in the mitochondria of cancer cells.…”

Oil-in-water biocompatible microemulsion as a carrier for the antitumor drug compound methyl dihydrojasmonate

“…The reactive oxygen species from MJ induces apoptosis in cancer cells through the generation of hydrogen peroxide and pro-apoptotic proteins of the Bcl-2 family. 13,14 The jasmonate derivatives have the ability to redifferentiate human myeloid leukemia cells through the activity of mitogen-activated protein kinase and cytokine isopentenyladenine. 10 The inhibition of angiogenesis was also described to contribute in cancer therapy.…”

“…4,5,14,31 Usually to solubilize MJ at such The in vivo antitumor activity of the MJ-loaded ME and the positive and negative controls was evaluated using Balb/c mice. The results of the tumor growth inhibition are shown in Figure 4.…”