Disruption of the hexokinase-VDAC complex for tumor therapy.
Unlike mitochondria from most normal tissues, cancer cell mitochondria demonstrate an association between the glycolytic enzyme hexokinase (HK) and the voltage-dependent anion channel (VDAC). This provides a therapeutic opportunity, as the association appears to protect tumor cells from mitochondrial outer membrane permeabilization (MOMP), an event that marks the point of no return in multiple pathways leading to cell death. In this issue of Oncogene, the plant hormone methyl jasmonate (MJ) is shown to disrupt the interaction between human HK and VDAC, causing the inhibition of glycolysis and the induction of MOMP. MJ has already been shown to have selective anticancer activity in preclinical studies, and this finding may stimulate the development of a novel class of small anticancer compounds that inhibit the HK-VDAC interaction.
Galluzzi
L
L
INSERM, U848, 39 rue C. Desmoulins, Villejuif, France.
Kepp
O
O
Tajeddine
N
N
Kroemer
G
G
D000085:Acetates / Q000627:therapeutic use; D003517:Cyclopentanes / Q000627:therapeutic use; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy*; D054883:Oxylipins / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism*
D000085:Acetates; D003517:Cyclopentanes; D046912:Multiprotein Complexes; D054883:Oxylipins; D010936:Plant Extracts; D050994:Voltage-Dependent Anion Channels; C072239:methyl jasmonate; D006593:Hexokinase