Abstract | BACKGROUND:
PC-SPES is a botanical preparation shown to have efficacy in patients with androgen-dependent and androgen-independent prostate carcinoma. Several herbal constituents in PC-SPES inhibit tumor growth through cell cycle arrest and apoptosis, although the mechanisms of these activities are poorly defined. We sought to identify PC-SPES-induced changes in gene expression, specifically in those genes encoding cytoskeletal proteins that could be associated with PC-SPES-induced cytoxicity. METHODS: RESULTS:
PC-SPES treatment of LNCaP cells for 24 hours altered the expression of 17 cytoskeletal genes. mRNA levels of alpha-tubulin decreased sevenfold. Although paclitaxel stabilized and PC-SPES treatment disrupted microtubule architecture in LNCaP cells, the combination of both agents had an intermediate effect. PC-SPES inhibited tubulin polymerization in vitro, even in the presence of paclitaxel. Compared with tumors in control mice (mean tumor volume = 2983 mm(3), 95% confidence interval [CI] = 2380 to 3586 mm(3)), tumors were statistically significantly smaller in mice that received PC-SPES (mean tumor volume = 2018 mm(3), 95% CI = 1450 to 2568 mm(3); P =.028), paclitaxel (mean tumor volume = 1340 mm(3), 95% CI = 697 to 1983 mm(3); P<.001), or the combination of PC-SPES and paclitaxel (mean tumor volume = 1955 mm(3), 95% CI = 1260 to 2650 mm(3); P =.034). CONCLUSION:
PC-SPES may interfere with microtubule polymerization. This activity has implications for the clinical management of patients with advanced prostate cancer who may be taking PC-SPES concurrently with microtubule-modulating chemotherapeutic agents, such as paclitaxel.
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Authors | Michael J Bonham, Anna Galkin, Bruce Montgomery, William L Stahl, David Agus, Peter S Nelson |
Journal | Journal of the National Cancer Institute
(J Natl Cancer Inst)
Vol. 94
Issue 21
Pg. 1641-7
(Nov 06 2002)
ISSN: 0027-8874 [Print] United States |
PMID | 12419791
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- Drugs, Chinese Herbal
- Plant Extracts
- Tubulin
- herbal preparation PC-SPES
- Paclitaxel
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Topics |
- Animals
- Antineoplastic Agents, Phytogenic
(therapeutic use)
- Cell Division
(drug effects)
- Drugs, Chinese Herbal
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Male
- Mice
- Mice, Nude
- Microtubules
(drug effects, ultrastructure)
- Oligonucleotide Array Sequence Analysis
- Paclitaxel
(therapeutic use)
- Phytotherapy
- Plant Extracts
(therapeutic use)
- Prostatic Neoplasms
(drug therapy, genetics, pathology)
- Transplantation, Heterologous
- Tubulin
(genetics, metabolism)
- Tumor Cells, Cultured
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