Novel resveratrol derivatives induce apoptosis and cause cell cycle arrest in prostate cancer cell lines.
BACKGROUND
Resveratrol (RV), a naturally occurring phytoalexin, exerts manifold biological effects against a variety of human tumor cell lines. In this study, the cytotoxic and biological effects of novel RV derivatives were investigated in prostate cancer cells.


METHODS
Cytotoxicity of the compounds was assessed by clonogenic assays in PC-3, LNCaP and DU-145 human prostate cancer cell lines. Induction of apoptosis was studied by Hoechst-propidium-iodide double staining. Cell cycle phase distribution of prostate cancer cells was analyzed using flow cytometry.


RESULTS
Methoxy- and hydroxy-substituted RV derivatives exerted cytotoxic effects against all three cell lines. The most potent compounds, 3,3',4,4',5,5'-hexahydroxy-stilbene and 3,4,4',5-tetramethoxystilbene, induced apoptosis at concentrations lower than RV and caused cell cycle arrest in the cell lines investigated.


CONCLUSIONS
Introducing additional hydroxy- and methoxymoieties to the stilbene ring of RV is capable of enhancing its cytotoxic and pro-apoptotic effects in hormone-responsive and non-responsive prostate cancer cells.
Horvath
Zsuzsanna
Z
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Waehringer Guertel 18-20, A-1090, Vienna, Austria.
Marihart-Fazekas
Sybille
S
Saiko
Philipp
P
Grusch
Michael
M
Ozsüy
Mehmet
M
Harik
Mike
M
Handler
Norbert
N
Erker
Thomas
T
Jaeger
Walter
W
Fritzer-Szekeres
Monika
M
Djavan
Bob
B
Szekeres
Thomas
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D010636:Phenols / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010636:Phenols; D013267:Stilbenes; D000077185:Resveratrol