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PC-SPES (PDQ®)

Laboratory/Animal/Preclinical Studies

Before the discovery of diethylstilbestrol (DES), warfarin, and indomethacin contamination, PC-SPES appeared to have some efficacy as an antineoplastic agent in laboratory and animal studies. These studies are presented below. Due to the fact that there was no standardization of the composition of PC-SPES or any knowledge of the amount of contamination of each lot used in testing, it is difficult to interpret the data from these studies.

In one study that attempted to measure the effects of the whole PC-SPES mixture versus that of individual herbs of PC-SPES on prostate-specific antigen (PSA) expression and cell growth, LNCaP cells were treated with ethanol extracts of PC-SPES and each of the eight herbs. The PC-SPES mixture reduced cell growth by 72% to 80%, while Dendranthema morifolium (Ramat.) Tzvelev (synonym Chrysanthemum morifolium) (chrysanthemum) produced the highest reduction of the herb group at 85%. Panax pseudo ginseng var. notoginseng Hoo & tseng (Synonym Panax notoginseng [Burkill] F.H.Chen) was next at 80.9% reduction, followed by Glycyrrhiza uralensis Fisch ex DC. (73%). The lowest reduction in cell growth was exhibited by Serenoa repens (Bartr.) Small (14.5%). Scutellaria baicalensis Georgi, Serenoa repens, and Glycyrrhiza uralensis lowered PSA expression, but each of the other herbs increased PSA expression. The ability of individual herbs to reduce PSA expression was not uniform, but the PC-SPES mixture as a whole exhibited a uniform response. The varying results with the individual herbs and the positive response of the cells (i.e., increased cytotoxicity and reduced PSA expression) to the aggregate PC-SPES mixture may suggest that the botanicals in PC-SPES work in concert and that no individual herb can account for the overall effects of the mixture.[1]

In other studies, PC-SPES was found to inhibit clonal growth in three human prostate cancer cell lines: LNCaP, PC-3, and DU-145. Cell cycle analysis showed cell cycle arrest at the G2 phase.[2] Cell proliferation and reduced clonogenicity were observed in cancer cell lines other than those of prostate cancer: human breast carcinoma lines MCF-7 and T47-D, SK-N-MC neuroepithelioma, COLO 38 melanoma, U937 histiomonocytic lymphoma, and HL-60 and MOLT-4 leukemias. Cytotoxic and cytostatic effects of PC-SPES were common to all tumor cell lines tested.[3]

In another study evaluating regulation of PSA expression and androgen receptor (AR) activity, LNCaP prostate cancer cell lines showed downregulation of both proliferating cell nuclear antigen (PCNA) and PSA expression. PSA changes occurred concurrently with the decrease of PCNA. The results suggest that PC-SPES modulates cell growth by changing PCNA expression and may decrease PSA levels indirectly by suppressing AR expression.[4]

None of the studies above indicated lot number or year of manufacture of the PC-SPES used. Therefore, it is not possible to assess the amount of contamination of the mixtures used in the studies or whether the mixtures used were not in fact contaminated.

A 1998 study that evaluated estrogenic activity of extracts of PC-SPES, ginseng (Panax ginseng C.A. Meyer), saw palmetto, DES, and estrone (estradiol -17 beta) in vitro reported on the estrogenic response of ovariectomized CD-1 mice to PC-SPES extract as well as the response to PC-SPES capsules in eight prostate cancer patients who had received previous therapy. [5] This study used four samples of PC-SPES ordered in separate purchases from BotanicLab. No lot numbers were supplied in the study. Lot numbers from October 1996 through July 1998 were later tested for contamination and had DES levels of 114.74 μg/g to 159.27 μg/g, as well as the highest detected levels of indomethacin of the PC-SPES lots tested.[6] In vitro tests of PC-SPES extract or estradiol showed estrogenic activity similar to 1 nM estradiol on estrogen receptor Y253 yeast strain. Transcriptional activation assays in yeast strain PL3 Saccharomyces cerevisiae with ethanolic extract of PC-SPES exhibited estrogen-like effects. In the eight prostate cancer patients, serum testosterone concentrations decreased during the use of PC-SPES and increased within 3 weeks after treatment was discontinued. PSA levels decreased in all eight patients. Side effects in all eight patients were similar to those seen after treatment with estrogen: breast tenderness and loss of libido. One patient had superficial venous thrombosis. In addition to baicalin, two other compounds purified from PC-SPES, isoliquiritigenin and wogonin, have been shown to reduce PSA levels and downregulate AR.[7]

By incorporating PC-SPES into the rat diet, researchers conducting an in vivo study showed antitumor effects using a Dunning R3327 rat prostate cancer model. Levels of 0.05% and 0.025% of dietary PC-SPES were fed to the rats over a 6-week period. No toxicity was seen, nor was there a difference in the food intake of the rats during this time. Pulmonary tumors were induced by intradermal injections of MAT-LyLu cells, which are particularly resistant to many forms of treatment. Tumor incidence was inhibited in a dose-dependent manner, and the rate of tumor growth showed the same dose-dependent response.[8,9]

In another study, which used male BNX nu/nu immunodeficient nude mice, PC-SPES was also administered orally, but in suspension. The mice received 300 rad of whole-body irradiation, after which they were inoculated with either PC-3 or DU-145 prostate cancer cell lines. Treatment with PC-SPES began the day after injection. Results showed that PC-SPES suppressed the growth of DU-145 tumors compared with tumor growth in the control group. Cytological analysis showed apoptosis in the treated group that was not apparent in the control group.[10]

In two other studies, clinical studies of patients were initiated along with in vitro and in vivo research. The results of these two patient groups are discussed in the Human/Clinical Trials section of this summary. The first study, preceding more extensive research, examined in vitro activity of PC-SPES against LNCaP, LNCaP-bcl-2, PC-3, and DU-145 cells lines. Results showed that PC-SPES was active in suppressing both hormone -sensitive and hormone-insensitive prostate cancer cell lines. In the subsequent study, research was conducted in vitro on the ability of PC-SPES to induce apoptosis in androgen-independent (AI) prostate cancer cell lines, and in vivo on the effect of oral PC-SPES on the growth of xenografted PC-3 tumors in immunodeficient male mice. Mice in the treatment arm—in which treatment was started 1 week after implantation—showed a significant decrease in tumor weight when compared with mice in the control arm. PC-SPES showed activity against both androgen -sensitive and AI prostate cancer in the patients and suppressed tumor growth in AI tumors in mice.[10-12] In both studies, the patients were given capsules manufactured between 1996 and 1999, a time when contamination levels of DES were highest.[6]

Another study in rats demonstrated that PC-SPES (one lot contaminated with DES and one lot without DES) caused some decrease in the activity of a liver enzyme involved in drug metabolism (CYP3A).[13]

References

  1. Hsieh TC, Lu X, Chea J, et al.: Prevention and management of prostate cancer using PC-SPES: a scientific perspective. J Nutr 132 (11 Suppl): 3513S-3517S, 2002. [PUBMED Abstract]
  2. Kubota T, Hisatake J, Hisatake Y, et al.: PC-SPES: a unique inhibitor of proliferation of prostate cancer cells in vitro and in vivo . Prostate 42 (3): 163-71, 2000. [PUBMED Abstract]
  3. Ko R, Wilson RD, Loscutoff S: PC-SPES. Urology 61 (6): 1292, 2003. [PUBMED Abstract]
  4. Hsieh TC, Wu JM: Mechanism of action of herbal supplement PC-SPES: elucidation of effects of individual herbs of PC-SPES on proliferation and prostate specific gene expression in androgen-dependent LNCaP cells. Int J Oncol 20 (3): 583-8, 2002. [PUBMED Abstract]
  5. 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]
  6. 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]
  7. Chen S, Gao J, Halicka HD, et al.: Down-regulation of androgen-receptor and PSA by phytochemicals. Int J Oncol 32 (2): 405-11, 2008. [PUBMED Abstract]
  8. Tiwari RK, Geliebter J, Garikapaty VP, et al.: Anti-tumor effects of PC-SPES, an herbal formulation in prostate cancer. Int J Oncol 14 (4): 713-9, 1999. [PUBMED Abstract]
  9. Geliebter J, Mittelman A, Tiwari RK: PC-SPES and prostate cancer. J Nutr 131 (1): 164S-166S, 2001. [PUBMED Abstract]
  10. de la Taille A, Buttyan R, Hayek O, et al.: Herbal therapy PC-SPES: in vitro effects and evaluation of its efficacy in 69 patients with prostate cancer. J Urol 164 (4): 1229-34, 2000. [PUBMED Abstract]
  11. 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]
  12. de la Taille A, Hayek OR, Buttyan R, et al.: Effects of a phytotherapeutic agent, PC-SPES, on prostate cancer: a preliminary investigation on human cell lines and patients. BJU Int 84 (7): 845-50, 1999. [PUBMED Abstract]
  13. Wadsworth T, Poonyagariyagorn H, Sullivan E, et al.: In vivo effect of PC-SPES on prostate growth and hepatic CYP3A expression in rats. J Pharmacol Exp Ther 306 (1): 187-94, 2003. [PUBMED Abstract]
  • Updated: February 5, 2014