CeReS-18 inhibits growth and induces apoptosis in human prostatic cancer cells

Polypeptide growth factors are positive and negative regulators of prostatic growth and function, and many positive regulators of growth in the prostate have been extensively studied. However, very few inhibitors of prostate cell proliferation have been identified. We have isolated a unique 18-kDa sialoglycopeptide (CeReS-18) which inhibits cell proliferation of three separate lines of human prostate cancer cells, as well as inducing cellular cytotoxicity via an apoptotic pathway unrelated to the Bcl-2 family of proteins.

Cell cycle inhibition was analyzed by direct cell counts with a Coulter (Miami, FL) cell counter. Apoptotic cells were analyzed by electron microscopy, annexin V-fluorescein isothiocyanate (FITC) staining, fluorescence microscopy, and propidium iodide uptake measured with a fluorescence-activated cell sorter. Expression of the proteins of the Bcl-2 family was detected by Western blot analysis.

We found that CeReS-18 inhibits cell proliferation of androgen-responsive, LNCaP.FGC human prostate cancer cells, as well as of androgen-nonresponsive DU-145 and PC3 human prostate cancer cells. Furthermore a, fivefold increase over the inhibitory concentration of CeReS-18 elicited a cytotoxic response by all three cell lines. We thus characterized the cytotoxic mechanism as apoptotic in nature, and we measured the expression of several members of the Bcl-2 family in PC3 cells upon treatment with CeReS-18.

The data indicate that CeReS-18 is a potent inhibitor of cellular progression through the cell cycle by both androgen-responsive and androgen-nonresponsive human prostate cancer cells. In addition, treatment of both types of cells with increased concentrations of CeReS-18 induces cellular cytotoxicity, characterized as apoptosis.