ROLE OF MAMMALIAN PARAOXONASES IN CELL PROLIFERATION AND APOPTOSIS OF TUMOR CELLS

Mammalian paraoxonase family comprises three highly conserved enzymes PON1, PON2, and PON3. PON1 and PON3 are present in serum lipoprotein fractions, however PON2 is an intracellular protein found in almost every tissue, particularly in the mitochondria, endoplasmic reticulum and perinuclear region. PONs are important anti-oxidative enzymes and hence detoxifying. Their roles in atherosclerosis, organophosphate degradation, diabetes, obesity and innate immunity have been established. Physiological substrate for PON2 is unknown, although it shows lactonase activity in vitro. The cytoprotective effect of PON2 through anti-apoptotic behavior is satisfactorily documented. However, the pathway by which PON2 reduces apoptosis is not clear. We have selected human hepatic carcinoma cell line (Huh7) to study the role of PON2 in cell proliferation and apoptosis. The Huh7 cells were grown with and without hydrogen peroxide (in the range of 0-50 μM) and anti-cancerous drug cis-platin (in the range of 50-100 μM) treatment. The control and treated cells were used to detect the level of PON2 expression by real time PCR. PON2 showed significantly reduced level of expression, which supports the previously reported anti-apoptotic behavior of PON2. Similarly the level PON2 also reduced when treated(in the range of 50-100µM) with drug SS209A (acetophenon compound) in Mcf-7 cell line. These studies on PON2 together with the previous reports suggest that PON2 stabilizes tumor cells, which could be a potential target for cancer treatment, however the exact mechanism is yet to be understood. 2) KEYWORDS: Oxidative stress, atherosclerosis, Paraoxonases (PON), HDL, inflammation, diabetes, cancer, reactive oxygen species, organophosphates, Quorum Quenching.