Cancer: Prostate, glioma, melanoma
Action: Radio-sensitizer
Anvirzel is an extract of Nerium oleander (L.) currently undergoing, as Anvirzelª Phase I clinical evaluation as a potential treatment for cancer. Two of the active components of Anvirzel are the cardiac glycosides, oleandrin and oleandrigenin.
Prostate Cancer
In continuing research on the anti-tumor 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.
Studies also were conducted with Anvirzel (a hot water extract of Nerium oleander, known as Anvirzelª) and ouabain (found in the ripe seeds of African plants Strophanthus gratus). 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. 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 anti-tumor activity of this novel treatment for cancer (Smith et al., 2001).
Radio-sensitizers; Prostate Cancer
In the present study Nasu et al. (2002) explored the relative radio-sensitization potential of oleandrin, a cardiac glycoside contained within the plant extract known as Anvirzelª. The data show that oleandrin produces an enhancement of sensitivity of PC-3 human prostate cells to radiation; at a cell survival of 0.1, the enhancement factor was 1.32. The magnitude of radio-sensitization depended on duration of exposure of cells to drug prior to radiation treatment.
While a radio-sensitizing effect of oleandrin was evident with only 1 hour of cell exposure to drug, the effect greatly increased with 24 hours of oleandrin pre-treatment.
Activation was greatest when cells were exposed simultaneously to oleandrin and radiation. Inhibition of caspase-3 activation with Z-DEVD-FMK abrogated the oleandrin-induced enhancement of radiation response suggesting that both oleandrin and radiation share a caspase-3 dependent mechanism of apoptosis in the PC-3 cell line.
Glioma, Melanoma
Twelve human tumor cell lines were chosen to examine determinants of human tumor cell sensitivity to cardiac glycosides. In vitro cell culture models of human glioma HF U251 and U251 cells as well as human parental and modified melanoma BRO cells were also included in these studies. Cardiac glycosides such as oleandrin, ouabain and bufalin increased expression of Na+, K+ -ATPase alpha 1 and therefore total Na+, K+ -ATPase activity, which is associated with increased cellular levels of glutathione. Additionally, an increased colony-forming ability was noted in cells with high levels of Na+, K+ -ATPase alpha 1 expression, suggesting that Na+, K+ -ATPase alpha 1 isoform may be actively involved in tumor growth and cell survival (Lin, Ho, & Newman, 2010)
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