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Molecular effects of the herbal compound PC-SPES: identification of activity pathways in prostate carcinoma
Michael Bonham1, Hugh Arnold, Bruce Montgomery
1Divisions of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Abstract:
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.
Insights
The herbal preparation PC-SPES shows promise for advanced prostate cancer by altering gene expression. It affects cell cycle and androgen receptor genes, suggesting a unique mechanism beyond estrogenic activity.
Area of Science:
- Molecular Biology
- Oncology
- Pharmacology
Background:
- Advanced prostate cancer shows substantial response to PC-SPES.
- PC-SPES exhibits estrogenic activity, but its mechanism is unclear.
Purpose of the Study:
- Identify gene expression changes in prostate cancer cells treated with PC-SPES.
- Compare PC-SPES effects to known estrogenic agents like diethylstilbestrol.
Main Methods:
- Utilized cDNA microarray analysis.
- Exposed LNCaP prostate carcinoma cells to PC-SPES and diethylstilbestrol.
Main Results:
- PC-SPES altered expression of 156 genes within 24 hours.
- Down-regulated key genes: cell cycle regulators, tubulins, and androgen receptor.
- PC-SPES demonstrated distinct gene expression profile compared to diethylstilbestrol.
Conclusions:
- PC-SPES possesses unique biological activities.
- Gene expression alterations in cell cycle, cell structure, and androgen response pathways may mediate PC-SPES cytotoxicity.
- Suggests novel therapeutic mechanisms for prostate cancer treatment.
