There is a general agreement that most of the
cancer cells switch over to aerobic glycolysis (Warburg effect) and upregulate
antioxidant enzymes to prevent oxidative stress induced apoptosis. Thus, there is an evolving view to target these metabolic alterations by novel
anticancer agents to restrict
tumor progression in vivo. Previously we have reported that when a non toxic dose (10 mg/kg bw i.p.) of a novel anticancer
ruthenium(II)-complex containing 4-carboxy
N-ethylbenzamide;
Ru(II)-CNEB, was administered to the Dalton's
lymphoma (DL) bearing mice, it regressed DL growth by inducing apoptosis in the DL cells. It also inactivated
M4-LDH (M4-lactate dehydrogenase), an
enzyme that drives anaerobic glycolysis in the
tumor cells. In the present study we have investigated whether this compound is able to modulate regulation of glycolytic inhibition-apoptosis pathway in the DL cells in vivo. We observed that
Ru(II)-CNEB could decline expression of the inducible form of
6-phosphofructo-2-kinase (iPFK2: PFKFB3), the master regulator of glycolysis in the DL cells. The complex also activated
superoxide dismutase (the H2O2 producing
enzyme) but declined the levels of
catalase and
glutathione peroxidase (the two H2O2 degrading
enzymes) to impose oxidative stress in the DL cells. This was consistent with the enhanced p53 level, decline in Bcl2/Bax ratio and activation of
caspase 9 in those DL cells. The findings suggest that
Ru(II)-CNEB is able to activate oxidative stress-apoptosis pathway via p53 (a
tumor supressor
protein) mediated repression of iPFK2, a key glycolytic regulator, in the DL cells in vivo.