© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 17, 1275-1280,
September 4, 2002
© 2002 Oxford University Press
ARTICLE |
Herbal Composition PC-SPES for Management of Prostate Cancer: Identification of Active Principles
Affiliations of authors: M. Sovak, University of California, San Diego, Radiology Research, and Biophysica Foundation, La Jolla, CA; A. L. Seligson, Biophysica Foundation; M. Konas, Interpharma Praha, Modrany, Czech Republic; M. Hajduch, Laboratory of Experimental Medicine, Department of Pediatrics, Palacky University, Olomouc, Czech Republic; M. Dolezal, Institute of Chemical Technology, Department of Food Chemistry and Analysis, Prague, Czech Republic; M. Machala, Veterinary Research Institute, Brno, Czech Republic; R. Nagourney, University of California, Irvine, and Rational Therapeutics, Long Beach, CA.
Correspondence to: Milos Sovak, M.D., UCSD School of Medicine, Radiology Research and Biophysica Foundation, 3333 N. Torrey Pines Ct., Ste. 100, La Jolla, CA 92037–1023 (e-mail: radiologyresearch{at}ucsd.edu).
Background: The herbal mixture PC-SPES, used to manage advanced prostate cancer, has proven thrombogenic and highly estrogenic in clinical trials. However, attempts to identify the active compounds in PC-SPES have yielded incongruous results. Moreover, warfarin was identified in the serum of a patient taking PC-SPES who experienced a bleeding disorder. To determine the active components in PC-SPES potentially responsible for these effects, we analyzed PC-SPES lots manufactured from l996 through mid-2001. Methods: Antineoplastic activity of PC-SPES and its individual component extracts was determined by colony-forming assays with several prostate cancer cell lines, and estrogenicity was determined by analyzing expression of an estrogen-responsive reporter gene in breast cancer cells. High-pressure liquid chromatography was used to isolate, identify, and quantify components of PC-SPES. Components were also identified by proton nuclear magnetic resonance, gas chromatography/mass spectrometry, and mass spectra analysis. Results: PC-SPES lots manufactured from 1996 through mid-1999 contained the synthetic compounds indomethacin (range = 1.07–13.19 mg/g) and diethylstilbestrol (range = 107.28–159.27 µg/g) and were two to six times more antineoplastic and up to 50 times more estrogenic than lots manufactured after the spring of 1999. In lots manufactured after mid-1999, gradual declines in the concentrations of indomethacin (from 1.56 to 0.70 mg/g), diethylstilbestrol (from 46.36 to 0.00 µg/g), and total phytosterols (from 0.586 to 0.085 mg/g) were observed. Warfarin was identified for the first time in lots manufactured after July 1998 (range = 341–560 µg/g). In the August 2001 lot, increases were found in concentrations of the natural products licochalcone A (from 27.6 to 289.2 µg/g) and baicalin (from 12.5 to 38.8 mg/g). Conclusions: The phytochemical composition of PC-SPES varied by lot, and chemical analyses detected various amounts of the synthetic drugs diethylstilbestrol, indomethacin, and warfarin and several natural products. To qualify for clinical pharmacologic exploration, nutritional supplements including herbal mixtures should meet standards of quality control under the Good Manufacturing Practice system, and the manufacturers of such supplements should provide reliable analytical quality assurance.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. B van Breemen, H. H. Fong, and N. R Farnsworth Ensuring the safety of botanical dietary supplements Am. J. Clinical Nutrition, February 1, 2008; 87(2): 509S - 513S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. R. Cassileth, G. E. Deng, J. E. Gomez, P. A. S. Johnstone, N. Kumar, and A. J. Vickers Complementary Therapies and Integrative Oncology in Lung Cancer: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition) Chest, September 1, 2007; 132(3_suppl): 340S - 354S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bonham, J. Posakony, I. Coleman, B. Montgomery, J. Simon, and P. S. Nelson Characterization of Chemical Constituents in Scutellaria baicalensis with Antiandrogenic and Growth-Inhibitory Activities toward Prostate Carcinoma Clin. Cancer Res., May 15, 2005; 11(10): 3905 - 3914. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Marcus and W. R. Snodgrass Do No Harm: Avoidance of Herbal Medicines During Pregnancy Obstet. Gynecol., May 1, 2005; 105(5): 1119 - 1122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Boullata Natural Health Product Interactions with Medication Nutr Clin Pract, February 1, 2005; 20(1): 33 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Kosty PC-SPES: Hope or Hype? J. Clin. Oncol., September 15, 2004; 22(18): 3657 - 3659. [Full Text] [PDF]
|
|
|
|
|
|
W. K. Oh, P. W. Kantoff, V. Weinberg, G. Jones, B. I. Rini, M. K. Derynck, R. Bok, M. R. Smith, G. J. Bubley, R. T. Rosen, et al. Prospective, Multicenter, Randomized Phase II Trial of the Herbal Supplement, PC-SPES, and Diethylstilbestrol in Patients With Androgen-Independent Prostate Cancer J. Clin. Oncol., September 15, 2004; 22(18): 3705 - 3712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sparreboom, M. C. Cox, M. R. Acharya, and W. D. Figg Herbal Remedies in the United States: Potential Adverse Interactions With Anticancer Agents J. Clin. Oncol., June 15, 2004; 22(12): 2489 - 2503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Mobley, J. O. L'Esperance, M. Wu, C. J. Friel, R. H. Hanson, and S.-M. Ho The novel estrogen 17{alpha}-20Z-21-[(4-amino)phenyl]-19-norpregna-1,3,5(10),20-tetraene-3,17{beta}-diol induces apoptosis in prostate cancer cell lines at nanomolar concentrations in vitro Mol. Cancer Ther., May 1, 2004; 3(5): 587 - 596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. R. Cassileth and G. Deng Complementary and Alternative Therapies for Cancer Oncologist, February 1, 2004; 9(1): 80 - 89. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ikezoe, Y. Yang, D. Heber, H. Taguchi, and H. P. Koeffler PC-SPES: A Potent Inhibitor of Nuclear Factor-{kappa}B Rescues Mice from Lipopolysaccharide-Induced Septic Shock Mol. Pharmacol., December 1, 2003; 64(6): 1521 - 1529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Wadsworth, H. Poonyagariyagorn, E. Sullivan, D. Koop, and C. E. Roselli In Vivo Effect of PC-SPES on Prostate Growth and Hepatic CYP3A Expression in Rats J. Pharmacol. Exp. Ther., July 1, 2003; 306(1): 187 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Piersen Phytoestrogens in Botanical Dietary Supplements: Implications for Cancer Integr Cancer Ther, June 1, 2003; 2(2): 120 - 138. [Abstract] [PDF]
|
|
|
|
|
|
S. Wilkinson and G. W. Chodak Critical Review of Complementary Therapies for Prostate Cancer J. Clin. Oncol., June 1, 2003; 21(11): 2199 - 2210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. L Larimore and D. P O'Mathuna Quality Assessment Programs for Dietary Supplements Ann. Pharmacother., June 1, 2003; 37(6): 893 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Marcus and A. P. Grollman Botanical Medicines -- The Need for New Regulations N. Engl. J. Med., December 19, 2002; 347(25): 2073 - 2076. [Full Text] [PDF]
|
|
|
|
 |
|
 W. A. Weiger, M. Smith, H. Boon, M. A. Richardson, T. J. Kaptchuk, and D. M. Eisenberg Advising Patients Who Seek Complementary and Alternative Medical Therapies for Cancer Ann Intern Med, December 3, 2002; 137(11): 889 - 903. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Bonham, A. Galkin, B. Montgomery, W. L. Stahl, D. Agus, and P. S. Nelson Effects of the Herbal Extract PC-SPES on Microtubule Dynamics and Paclitaxel-Mediated Prostate Tumor Growth Inhibition J Natl Cancer Inst, November 6, 2002; 94(21): 1641 - 1647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. White PC-SPES-A Lesson for Future Dietary Supplement Research J Natl Cancer Inst, September 4, 2002; 94(17): 1261 - 1262. [Full Text] [PDF]
|
|