Methyl jasmonate binds to and detaches mitochondria-bound hexokinase

Disruption of the hexokinase–VDAC complex for tumor therapy

“…MJ induced large amplitude swelling (which is indicative of PTPC opening) when added to mitochondria purified from the rat brain or liver (the only normal tissues in which VDAC and HK interact in physiological conditions). These observations correlated also with the fact that MJ was shown to promote signs of MOMP (such as cytochrome c release) in cancer cell lines and that MJ-induced cell death could be inhibited by transfection-enforced overexpression of HK (Goldin et al, 2008).…”

“…Irrespective of the morphological appearance of endstage cell death (apoptotic, necrotic, autophagic or mitotic), mitochondrial outer membrane permeabilization (MOMP) is frequently the decisive event that delimits the frontier between survival and death (Ferri and Kroemer, 2001). New agents that facilitate MOMP in tumor cells, hence, are potentially useful for the treatment of cancer, as is suggested for methyl jasmonate (MJ) in this issue of Oncogene (Goldin et al, 2008).…”

Methyl jasmonate and its potential in cancer therapy

“…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.…”

“…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.…”

“…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. 10 Moreover, it has been shown that only 80% of hexokinase II is associated with mitochondria. 11 Therefore, there is still a potential risk in the application of MeJa in clinical cancer therapies, especially considering the fact that hexokinase I and hexokinase II are also expressed in normal brain, kidney, heart and skeletal tissues.…”