In 1997, the herbal formula for PC-SPES was patented in the United States. A company, BotanicLab (Brea, California), was formed to produce, distribute, and sell the product. PC-SPES was sold through the BotanicLab Web site (the Web site was taken down after PC-SPES was recalled) and through selected distributors. Anecdotal information about the product and its positive effects was widely circulated on the Internet through Web sites that informed prostate cancer patients about new developments in treatment. At the same time, the published papers were being read by the scientific community, and the findings were presented at various conferences. As a result, clinicians and researchers began looking at PC-SPES as one of the first viable treatments to come out of the alternative medicine community.
The manufacturing process for PC-SPES has been described by the manufacturer as follows: extracts of raw plant material were obtained from the specified plants, which were grown in particular geographic regions in China and harvested at certain times of the year to reduce the natural variation inherent in any biological product. The extracts were shipped to the United States, where high-performance liquid chromatography (HPLC) was used to monitor the key active compounds—which are believed to be directly related to the clinical effects—for batch-to-batch reproducibility. Activity-related biomarkers were kept in a constant concentration from lot to lot. A commercial testing laboratory (Truesdail Laboratory; Tustin, California) was used to guarantee that each batch was free from contamination with heavy metals, pesticides, microorganisms and products, and prescription drugs. Each lot was standardized by an anticancer bioassay for an effective dose of 50% in vitro inhibition of cell growth using human LNCaP cells for androgen-dependent (AD) prostate cancer and DU-145 cells for androgen-independent (AI) prostate cancer. The powder was then encapsulated, bottled, labeled, and sterilized at the BotanicLab facility.
In 2001, allegations that PC-SPES contained the synthetic estrogen diethylstilbestrol (DES) started to appear on e-mail listservs used by prostate cancer patients and in online newsletters. Prostate cancer patients who were taking PC-SPES noticed that their recent medication was not as effective as the previous batches. A sample of PC-SPES submitted to a testing laboratory by BotanicLab in August 2001 found no DES. BotanicLab posted the letter from the laboratory on their Web site, claiming that PC-SPES contained no DES. However, in other tests of six different lots of PC-SPES received from two different sources in August 2001, Rocky Mountain Instrumental Laboratory found varying amounts of DES in three lots. More tests done by the California Department of Health Services in February 2002 did not find DES but did find warfarin, a prescription drug used as a blood thinner.
The presence of a synthetic estrogen such as DES was suspected early in the clinical use of PC-SPES after reports in the literature discussed the mixture’s estrogen-like ability to lower prostate-specific antigen (PSA) levels in AD prostate cancer patients. In addition, the side effects of treatment were similar to those of estrogen therapy. [5-7] In one study, patients who showed the most response to PC-SPES were also those who were the most responsive to DES.[8,9] The same study also attempted to find out whether DES or similar compounds were present in PC-SPES. Transcriptional activation assays in yeast strain PL3 Saccharomyces cerevisiae using an ethanolic extract of PC-SPES showed estrogenic activity similar to 1nM estradiol. In addition, ovariectomized CD-1 mice showed substantially increased uterine weights. HPLC, gas chromatography, and mass spectrometry did not reveal the presence of DES but rather that of a compound with similar chemical characteristics. The authors of the report concluded that PC-SPES contains estrogenic compounds that are distinct from DES or other synthetic estrogens.
A definitive evaluation of PC-SPES analyzed specific lots of PC-SPES capsules manufactured from 1996 to 2001. In addition to using HPLC to isolate, identify, and quantify the synthetic drugs and active phytoestrogens, this study also identified components using proton nuclear magnetic resonance, gas chromatography/mass spectrometry, and mass spectra analysis. Tests showed the presence of the synthetic drugs indomethacin (a nonsteroidal anti-inflammatory drug not previously reported in the literature or found in other testing), DES, and warfarin. Testing was also done for concentrations of the two naturally occurring phytosterols, licochalcone A and baicalin. Test results indicated a history of rising and falling levels of contamination by the three synthetic drugs and a recent rise in the naturally occurring phytochemicals in PC-SPES. Lots of PC-SPES manufactured in 1996 through mid-1999 contained indomethacin ranging from 1.07 mg/g to 13.19 mg/g and DES ranging from 107.28 µg/g to 159.27 µg/g and were 2 to 6 times more antineoplastic and up to 50 times more estrogenic than lots manufactured after the spring of 1999. In vitro testing of ethanolic extracts of PC-SPES against LNCaP, PC-3, and DU-145 prostate cancer cell lines showed a decrease in both antineoplasticity and estrogenicity in lots of PC-SPES manufactured in June 1998 through August 2001, which correlated with the amount of DES and indomethacin contamination. Another in vitro test of suspected lots of PC-SPES manufactured from 2000 to 2001 also showed the presence of DES.
Although the laboratory testing showed that certain lots of the mixture contained indomethacin, warfarin, and DES, the amount of DES present may not have accounted for all of the estrogenic effect of PC-SPES. There is some evidence that the mixture acts differently from DES at the molecular level.[12,13] In addition, its anticancer effects on both AI prostate cancer and AD prostate cancer may point to a mechanism other than estrogen-like activity.[10,14,15] The in vitro activity of PC-SPES against cancer cells other than prostate also gives rise to the speculation that its estrogen-like qualities might not account for all of the mixture’s anticancer activity.[16,17]
- Chen S, Wang X: Herbal Composition for Treating Prostate Carcinoma. US Patent 5665393. September 9, 1997. Washington, DC: US Patent and Trademark Office, 1997. Available online. Last accessed February 5, 2014.
- Marks LS, DiPaola RS, Nelson P, et al.: PC-SPES: herbal formulation for prostate cancer. Urology 60 (3): 369-75; discussion 376-7, 2002. [PUBMED Abstract]
- PSA Rising: Prostate Cancer Survivor News, Info and Support. New York, NY: PSA Rising, 2005. Available online. Last accessed February 5, 2014.
- Ko R, Wilson RD, Loscutoff S: PC-SPES. Urology 61 (6): 1292, 2003. [PUBMED Abstract]
- Oh WK, George DJ, Hackmann K, et al.: Activity of the herbal combination, PC-SPES, in the treatment of patients with androgen-independent prostate cancer. Urology 57 (1): 122-6, 2001. [PUBMED Abstract]
- Oh WK, George DJ, Kantoff PW: Rapid rise of serum prostate specific antigen levels after discontinuation of the herbal therapy PC-SPES in patients with advanced prostate carcinoma: report of four cases. Cancer 94 (3): 686-9, 2002. [PUBMED Abstract]
- de la Taille A, Hayek OR, Burchardt M, et al.: Role of herbal compounds (PC-SPES) in hormone-refractory prostate cancer: two case reports. J Altern Complement Med 6 (5): 449-51, 2000. [PUBMED Abstract]
- Pirani JF: The effects of phytotherapeutic agents on prostate cancer: an overview of recent clinical trials of PC SPES. Urology 58 (2 Suppl 1): 36-8, 2001. [PUBMED Abstract]
- DiPaola RS, Zhang H, Lambert GH, et al.: Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer. N Engl J Med 339 (12): 785-91, 1998. [PUBMED Abstract]
- Sovak M, Seligson AL, Konas M, et al.: Herbal composition PC-SPES for management of prostate cancer: identification of active principles. J Natl Cancer Inst 94 (17): 1275-81, 2002. [PUBMED Abstract]
- Guns ES, Goldenberg SL, Brown PN: Mass spectral analysis of PC-SPES confirms the presence of diethylstilbestrol. Can J Urol 9 (6): 1684-8; discussion 1689, 2002. [PUBMED Abstract]
- Chen S, Ruan Q, Bedner E, et al.: Effects of the flavonoid baicalin and its metabolite baicalein on androgen receptor expression, cell cycle progression and apoptosis of prostate cancer cell lines. Cell Prolif 34 (5): 293-304, 2001. [PUBMED Abstract]
- Bonham M, Arnold H, Montgomery B, et al.: Molecular effects of the herbal compound PC-SPES: identification of activity pathways in prostate carcinoma. Cancer Res 62 (14): 3920-4, 2002. [PUBMED Abstract]
- Reynolds T: Contamination of PC-SPES remains a mystery. J Natl Cancer Inst 94 (17): 1266-8, 2002. [PUBMED Abstract]
- Malkowicz SB: The role of diethylstilbestrol in the treatment of prostate cancer. Urology 58 (2 Suppl 1): 108-13, 2001. [PUBMED Abstract]
- Huerta S, Arteaga JR, Irwin RW, et al.: PC-SPES inhibits colon cancer growth in vitro and in vivo. Cancer Res 62 (18): 5204-9, 2002. [PUBMED Abstract]
- Schwarz RE, Donohue CA, Sadava D, et al.: Pancreatic cancer in vitro toxicity mediated by Chinese herbs SPES and PC-SPES: implications for monotherapy and combination treatment. Cancer Lett 189 (1): 59-68, 2003. [PUBMED Abstract]