A bioenergetic theory of prostate
malignancy proposed that normal
citrate-producing prostate epithelial cell become
citrate-oxidizing cells, in which mitochondrial
aconitase (mACON) is not limiting, providing the energy required for the onset and progression of
malignancy and
metastasis. However, no direct evidence has been approved to support the hypothesis. A full-length
cDNA encoding human skeletal muscle mACON
cDNA was cloned and sequenced. mACON
cDNA contains 19-bp
5' untranslated region, a 2343-bp coding segment, and 376-bp
3' untranslated region. This
precursor enzyme contains mitochondrial targeting sequence of 27
amino acid residues and mature
enzyme of 753
amino acids residues. A human anti-mACON overexpression vector containing the 1171-bp mACON
cDNA fragment in the reverse orientation was stable transfected into human prostate
carcinoma cells, PC-3 and DU145 cells. Results showed that mACON antisense blocked 40-60% mACON expression and enzymatic activity which induced decrease in the intracellular
ATP biosynthesis but increase
citrate secretion in the human prostate
carcinoma cells. mACON antisense-transfected cells have lower cell proliferation ratio than the mock of
DNA-transfected cells. Our study demonstrated the key role of the mACON in the cellular bioenergy and cell proliferation of human prostate
carcinoma cells.