Molecular effects of the herbal compound PC-SPES: identification of activity pathways in prostate carcinoma.
Clinical trials of the herbal preparation PC-SPES have demonstrated substantial responses in patients with advanced prostate cancer. Biochemical assays and clinical observations suggest that the effects of PC-SPES are mediated at least in part through estrogenic activity, although the mechanism(s) remains largely undefined. In this study, we used cDNA microarray analysis to identify gene expression changes in LNCaP prostate carcinoma cells exposed to PC-SPES and estrogenic agents including diethylstilbestrol. PC-SPES altered the expression of 156 genes after 24 h of exposure. Of particular interest, transcripts encoding cell cycle-regulatory proteins, alpha- and beta-tubulins, and the androgen receptor were down-regulated by PC-SPES. A comparison of gene expression profiles resulting from these treatments indicates that PC-SPES exhibits activities distinct from those attributable to diethylstilbestrol and suggests that alterations in specific genes involved in modulating the cell cycle, cell structure, and androgen response may be responsible for PC-SPES-mediated cytotoxicity.
Bonham
Michael
M
Divisions of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Arnold
Hugh
H
Montgomery
Bruce
B
Nelson
Peter S
PS
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D004054:Diethylstilbestrol / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D004968:Estrogens, Non-Steroidal; D010936:Plant Extracts; D011944:Receptors, Androgen; C114209:herbal preparation PC-SPES; D004054:Diethylstilbestrol