Clinical and Biologic Activity of an Estrogenic Herbal Combination (PC-SPES) in Prostate Cancer

DiPaola, Robert S.; Zhang, Huayan; Lambert, George H.; Meeker, Robert J.; Licitra, Edward J.; Rafi, Mohamed; Zhu, Bao Ting; Spaulding, Heidi; Goodin, Susan; Toledano, Michel B.; Hait, William N.; Gallo, Michael A.

doi:10.1056/nejm199809173391201

Cited by 271 publications

(88 citation statements)

References 21 publications

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“…Hepatotoxicity and other complications arising from herbal remedies containing undeclared pharmaceutical compounds (e.g., nonsteroidal antiinflammatory agents) have been well documented (42,43). Potent estrogenic activity has been documented in unregulated herbal nutritional supplements (44), and this component may have the potential to exacerbate lupus activity. Also of substantial clinical importance are the serious sequelae in patients with more severe disease who use unproven alternative remedies as a substitute for conventional treatment (11).…”

Section: Discussionmentioning

confidence: 99%

The use of alternative medical therapies in patients with systemic lupus erythematosus

Moore

Petri

Manzi

et al. 2000

Arthritis & Rheumatism

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Objective. As part of an ongoing study of health resource utilization and diminished productivity in patients with systemic lupus erythematosus (SLE), the use of alternative medical therapies was assessed. Methods. A cohort of 707 patients with SLE from 3 countries completed questionnaires on demographics, social support, health status (using the Short Form 36 health survey), satisfaction with health care, health resource utilization (conventional resources and alternative therapies), and time losses in labor market and non-labor market activities. Annual direct and indirect costs (1997 Canadian dollars) were calculated and compared for users and nonusers of alternative medical therapies. Results. Among the 707 patients, 352 (49.8%) were found to use alternative therapies and at similar rates across Canada, the United States, and the United Kingdom. Users were younger and better educated than nonusers, exhibited poorer levels of self-rated health status and satisfaction with medical care, and had minimal to no objective evidence of worse disease (ac-cording to the revised Systemic Lupus Activity Measure instrument). The mean of log direct medical costs for conventional resources was higher for users of select alternative therapies compared with nonusers. In a logistic regression, neither the number of alternative therapies used nor the individual therapy increased the probability of incurring indirect costs. Conclusion. The use of alternative medical therapies is common in patients with SLE. Users of many alternative medical therapies accrue greater conventional medical costs compared with nonusers. The use of alternative medical therapy may be a marker for care-seeking behavior associated with higher consumption of conventional medical resources in the absence of de-monstrable additional morbidity and should be considered in future cost analyses of patients with SLE.

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Section: Discussionmentioning

confidence: 99%

The use of alternative medical therapies in patients with systemic lupus erythematosus

Moore

Petri

Manzi

et al. 2000

Arthritis & Rheumatism

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“…In view of the known estrogenic compounds found in PC-SPES (DiPaola et al, 1998), two standards were used for the HPLC: 17b-estradiol and diadzein. Two standards were prepared by dissolving o0.5 mg in 50:50 H 2 O:ACN (1 ml).…”

Section: Hplc and Spectroscopymentioning

confidence: 99%

“…In stark contrast, one product stands out both for its clinically documented effects as well as its popularity among patients. PC-SPES (Botaniclab, Brea, CA, USA), a combination of eight herbs, has been shown to decrease prostate-specific antigen levels (PSA) >50% in many patients with androgen-independent prostate cancer (AIPC) (DiPaola et al, 1998;de la Taille et al, 2000;Small et al, 2000;Oh et al, 2001). This magnitude of PSA decrease has in turn been associated with improved survival in clinical trials (Bubley et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Gene profiling and promoter reporter assays: Novel tools for comparing the biological effects of botanical extracts on human prostate cancer cells and understanding their mechanisms of action

Bigler

Gulding

Dann³

et al. 2003

Oncogene

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The use of botanical mixtures is commonplace in patients with prostate cancer, yet the majority of these products have not been rigorously tested in clinical trials. Here we use PC-SPES, a combination of eight herbs that has been shown to be effective in clinical trials in patients with prostate cancer, as a model system to demonstrate 'proof of principle' as to how gene expression profiling coupled with promoter assays can evaluate the effect of herbal cocktails on human prostate cancer. In addition, we demonstrate how such approaches may be used for standardization of herbal extract activity by comparing the gene profile of PC-SPES with that of PC-CARE, a product with a similar herbal composition. Since prior studies have shown that PC-SPES contains estrogenic organic compounds, and such compounds are known to affect prostate cancer, an important issue is whether these are the primary drivers of the gene profile. Our data suggest that gene expression profiles of LNCaP human prostate cancer cells in response to PC-SPES are different from those found when diethylstilbestrol (DES), a synthetic estrogen, is used, suggesting that the estrogenic moieties within PC-SPES do not drive this expression signature. In contrast, the expression profile of PC-CARE was almost identical to that of DES, highlighting that mixtures containing similar herbal compositions do not necessarily result in similar biological activities. Interestingly, these three agents cause similar in vitro morphological changes and growth effects on LNCaP. To validate the expression profiling data, we evaluated the protein expression and promoter activity of prostate-specific antigen (PSA), a gene induced by PC-SPES but repressed by DES. In order to gain a mechanistic understanding of how PC-SPES and DES affect PSA expression differently, LNCaP cells were transiently transfected with wild-type and mutagenized PSA promoter, ARE concatemers and appropriate controls. We provide evidence that androgen response elements (ARE) II and III within the promoter region are responsible for the suppressive effects of DES and stimulatory effects of PC-SPES. In addition, we show that the effects on PSA transcription are ARE specific in the case of DES while PC-SPES affects this promoter nonspecifically. In conclusion, expression profiling coupled with mechanistic target validation yield valuable clues as to the mode of action of complex botanical mixtures and provides a new way to compare objectively mixtures with similar components either for effect or quality assurance prior to their use in clinical trials.

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“…The name PC-SPES comes from PC for prostate cancer and SPES, Latin for hope. Extracts of PC-SPES have demonstrated estrogenic effects [29] and decreased the growth of hormonesensitive as well hormone-insensitive prostate cancer cells [30]. Our results suggest that these effects might be related to not only the anticancer effects of G. lucidum but also its anti-androgen effects.…”

Section: A-reductase Inhibitory Activity Of Each Isolated Compound mentioning

confidence: 58%

Anti‐Androgen Effects of Extracts and Compounds from Ganoderma lucidum

Liu

Tamura

Kurashiki

et al. 2009

Chemistry & Biodiversity

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The 30% EtOH extracts of Ganoderma lucidum Fr. Karst (Ganodermateceae) showed weak 5alpha-reductase inhibitory activity and binding ability to androgen receptor. When LNCaP (lymph-node carcinoma of the prostate) cells were treated with the EtOH extracts, cell proliferation was inhibited. Treatment with the extracts significantly inhibited the testosterone-induced growth of the ventral prostate in castrated rats. These results showed that G. lucidum might be a useful ingredient in the treatment of androgen-induced diseases, such as benign prostatic hyperplasia or prostate cancer. From the 30% EtOH extracts, we isolated ganoderiol F, which showed binding activity to androgen receptor and inhibited LNCaP cell proliferation, as one of the active compounds in the 30% EtOH extracts.

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Clinical and Biologic Activity of an Estrogenic Herbal Combination (PC-SPES) in Prostate Cancer

Abstract: PC-SPES has potent estrogenic activity. The use of this unregulated mixture of herbs may confound the results of standard or experimental therapies and may produce clinically significant adverse effects.

Cited by 271 publications

References 21 publications

The use of alternative medical therapies in patients with systemic lupus erythematosus

The use of alternative medical therapies in patients with systemic lupus erythematosus

Gene profiling and promoter reporter assays: Novel tools for comparing the biological effects of botanical extracts on human prostate cancer cells and understanding their mechanisms of action

Anti‐Androgen Effects of Extracts and Compounds from Ganoderma lucidum

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