Inhibition of export of fibroblast growth factor-2 (FGF-2) from the prostate cancer cell lines PC3 and DU145 by Anvirzel and its cardiac glycoside component, oleandrin

Citation
Ja. Smith et al., Inhibition of export of fibroblast growth factor-2 (FGF-2) from the prostate cancer cell lines PC3 and DU145 by Anvirzel and its cardiac glycoside component, oleandrin, BIOCH PHARM, 62(4), 2001, pp. 469-472
Citations number
16
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
62
Issue
4
Year of publication
2001
Pages
469 - 472
Database
ISI
SICI code
0006-2952(20010815)62:4<469:IOEOFG>2.0.ZU;2-9
Abstract
Anvirzel is an extract of Nerium oleander currently undergoing Phase I clin ical evaluation as a potential treatment for cancer. Two of the active comp onents of Anvirzel are the cardiac glycosides oleandrin and oleandrigenin. Previous studies have demonstrated that, in vitro, cardiac glycosides may i nhibit fibroblast growth factor-2 (FGF-2) export through membrane interacti on with the Na+,K+-ATPase pump. In continuing research on the antitumor act ivity of this novel plant extract, the relative abilities of oleandrin and oleandrigenin to inhibit FGF-2 export from two human prostate cancer cell l ines, DU145 and PC3, were examined. An ELISA assay was utilized to determin e the FGF-2 concentration in the cell culture medium before and after expos ure to cardiac glycosides or the parent extract material Anvirzel. Both cel l 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 conc entrations (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 r elease from cells required continuous incubation for 48-72 hr; shorter incu bation times were not effective. These results demonstrate that Anvirzel, l ike oleandrin, inhibited FGF-2 export in vitro from PC3 and DU145 prostate cancer cells in a concentration- and time-dependent fashion and may, theref ore, contribute to the antitumor activity of this novel treatment for cance r. (C) 2001 Elsevier Science Inc. All rights reserved.