This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kiviharju, T. M. Articles by Peehl, D. M. Search for Related Content PubMed PubMed Citation Articles by Kiviharju, T. M. Articles by Peehl, D. M.

Antiproliferative and Proapoptotic Activities of Triptolide (PG490), a Natural Product Entering Clinical Trials, on Primary Cultures of Human Prostatic Epithelial Cells¹

Department of Urology, Stanford University School of Medicine, Stanford, California 94305

Interest in exploiting traditional medicines for prevention or treatment of cancer is increasing. Extracts from the herb Tripterygium wilfordii hook F have been used in China for centuries to treat immune-related disorders. Recently it was reported that triptolide (PG490), a purified compound from Tripterygium, possessed antitumor properties and induced apoptosis by p53-independent mechanisms in a variety of malignant cell lines. This property of triptolide attracted our attention because we have found that primary cultures of human prostatic epithelial cells derived from normal tissues and adenocarcinomas are in general extremely resistant to apoptosis. Furthermore, the function of wild-type p53 is impaired in these cells such that drugs that require p53 activity to induce cell death are ineffective. Therefore, the properties of triptolide and the recent approval of its water-soluble form (PG490-88) for entry into Phase I clinical trials suggested that this drug was a promising candidate to test for antitumor activity against prostate cells. Experiments presented here demonstrated that triptolide had dose-dependent effects on both normal and cancer-derived primary cultures of human prostatic epithelial cells. Low concentrations of triptolide inhibited cell proliferation and induced a senescence-like phenotype. Higher concentrations of triptolide induced apoptosis that was unexpectedly associated with nuclear accumulation of p53. Paradoxically, levels of the p53 target genes, p21^WAF1/CIP1 and hdm-2, were reduced, as was bcl-2. Our preclinical studies suggest that triptolide might be an effective preventive as well as therapeutic agent against prostate cancer and that triptolide may activate a functional p53 pathway in prostate cells.

This article has been cited by other articles:

				S. J. Leuenroth and C. M. Crews Triptolide-Induced Transcriptional Arrest Is Associated with Changes in Nuclear Substructure Cancer Res., July 1, 2008; 68(13): 5257 - 5266. [Abstract] [Full Text] [PDF]

				B. Z. Carter, D. H. Mak, W. D. Schober, M. F. Dietrich, C. Pinilla, L. T. Vassilev, J. C. Reed, and M. Andreeff Triptolide sensitizes AML cells to TRAIL-induced apoptosis via decrease of XIAP and p53-mediated increase of DR5 Blood, April 1, 2008; 111(7): 3742 - 3750. [Abstract] [Full Text] [PDF]

				W. Wang, S. Yang, Y. Su, Z. Xiao, C. Wang, X. Li, L. Lin, B. M. Fenton, S. F. Paoni, I. Ding, et al. Enhanced Antitumor Effect of Combined Triptolide and Ionizing Radiation Clin. Cancer Res., August 15, 2007; 13(16): 4891 - 4899. [Abstract] [Full Text] [PDF]

				S. J. Leuenroth, D. Okuhara, J. D. Shotwell, G. S. Markowitz, Z. Yu, S. Somlo, and C. M. Crews Triptolide is a traditional Chinese medicine-derived inhibitor of polycystic kidney disease PNAS, March 13, 2007; 104(11): 4389 - 4394. [Abstract] [Full Text] [PDF]

				B. Z. Carter, D. H. Mak, W. D. Schober, T. McQueen, D. Harris, Z. Estrov, R. L. Evans, and M. Andreeff Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway in leukemic cells Blood, July 15, 2006; 108(2): 630 - 637. [Abstract] [Full Text] [PDF]

				D M Peehl Primary cell cultures as models of prostate cancer development Endocr. Relat. Cancer, March 1, 2005; 12(1): 19 - 47. [Abstract] [Full Text] [PDF]