Anvirzel is an extract of Nerium oleander currently undergoing Phase I clinical evaluation as a potential treatment for
cancer. Two of the active components of
Anvirzel are the
cardiac glycosides oleandrin and
oleandrigenin. Previous studies have demonstrated that, in vitro,
cardiac glycosides may inhibit
fibroblast growth factor-2 (FGF-2) export through membrane interaction with the Na(+),K(+)-
ATPase pump. In continuing research on the antitumor activity of this novel
plant extract, the relative abilities of
oleandrin and
oleandrigenin to inhibit
FGF-2 export from two human
prostate cancer cell lines, DU145 and PC3, were examined. An ELISA assay was utilized to determine the
FGF-2 concentration in the cell culture medium before and after exposure to
cardiac glycosides or the parent extract material
Anvirzel. Both cell lines were exposed to non-cytotoxic concentrations of
oleandrin (0.05 and 0.1 ng/mL) for up to 72 hr. Studies also were conducted with
Anvirzel and
ouabain.
Oleandrin (0.1 ng/mL) produced a 45.7% inhibition of
FGF-2 release from PC3 cells and a 49.9% inhibition from DU145 cells. Non-cytotoxic concentrations (100 ng/mL) of
Anvirzel produced a 51.9 and 30.8% inhibition of
FGF-2 release, respectively, in the two cell lines. The decrease in
FGF-2 release from cells required continuous incubation for 48--72 hr; shorter incubation times were not effective. These results demonstrate that
Anvirzel, like
oleandrin, inhibited
FGF-2 export in vitro from PC3 and DU145
prostate cancer cells in a concentration- and time-dependent fashion and may, therefore, contribute to the antitumor activity of this novel treatment for
cancer.