D-4F, an apoA-I mimetic peptide, inhibits the proliferation and tumorigenicity of epithelial
ovarian cancer cells by upregulating the antioxidant enzyme MnSOD
Zahra Mojallal-Tabatabaei1
1. Department of Biochemistry, Institute of Biochemistry and Biophysics (IBB), Tehran
University, Tehran, Iran.
Abstract
Peptidomemtics have opened up a new horizon to combat cancer cells. Recent studies indicated
that both apoA-I and apoA-I memtic peptides impede the development of flank tumors in mice.
Using an animal model, in order to illuminate the mechanism(s) action of apoA-I mimetic
peptides underlying in tumor development, the effect of D-4F (an apoA-I mimetic peptide) on
the antioxidant status, the gene expression, function of antioxidant enzymes in ID8 cells (a
mouse epithelial ovarian cancer cell line) was evaluated. The study showed that D-4F treatment
not only reduced the viability and proliferation of ID8 cells, but also improved the antioxidant
status of ID8 cells as measured by lipid peroxidation, protein carbonyl, superoxide anion and
hydrogen peroxide levels. In line with this, treatment with D-4F induced MnSOD (but not
CuZnSOD) at the levels of mRNA and its cognate protein. To corroborate the notorious effect of
MnSOD, shRNA vectors were used to damper the inhibitory effects of D-4F on ID8 which
showed that the cell viability and proliferation reversed. Altogether, the results imply that the
inhibitory effects of D-4F on ID8 cell proliferation and tumor development may be mediated by
the induced expression and activity of MnSOD.
Key Words: Apolipoprotein A-I; oxidative stress; mimetic peptides; epithelial ovarian cancer
Reference
Ganapath E, et al. D-4F, an apoA-I mimetic peptide, inhibits proliferation and tumorigenicity of
epithelial ovarian cancer cells by upregulating the antioxidant enzyme MnSOD. International
Journal of Cancer 2012; 130: 1071–1081.