Should CM be subject to systematic scientific investigation?

[Guest guest]

Hi All, & Hi Wainright,

 

[susan, if the VBMA server bounces this because of size, could

YOU please mount it for me. IMO, Westerm Medicine has reached

an impasse in the Tx of prostate cancer [PC] and serious work, at

last, is being directed to herbal medicine in PC Tx.]

 

Wainright wrote:

> ... if we wish Chinese medicine as we know it to survive ...

 

IMO, Chinese medicine WILL survive, but NOT as we know it now!

CM will evolve to embrace established [and yet to be established]

medical and social facts from the West.

 

Parallel with the evolution of CM, we will probably see evolution in

Western medicine (WM) to embrace established [and yet to be

established] medical and social facts from the East.

 

In the evolutions of CM and WM, we will see more and more cross-

linkages - integration - so that in time the two systems will grow

closer and closer together. It remains to be seen whether this will

take 5, 50, 500, or 5000 years, but sooner or later we will have an

integrated medicine of the best available.

 

> ... an important task is for us to exert political pressure to NOT

> subject CM to any type of systematic scientific investigation ...

 

With respect, I disagree. IMO, systematic scientific investigation

offers the BEST hope for the development of effective, objective

medicine. It will identify and eliminate (or correct) the fallacies and

will highlight and improve the effective methods.

 

> ... or at the very least, to preserve a high measure of autonomy

> for CM in the process. Wainwright

 

Wainright, in developing my argument, I will use recent references

from Medline on prostate cancer.

 

Thomson et al (2002) wrote: " Because of the woeful ineffectiveness

of standard treatment modalities on the overall survival rate from PC

in the past 50 years, a more radical approach to the treatment of

this cancer is justified " . By " radical approach " , they meant

consideration of herbal medicine - in this case PC-SPES!!

 

I agree if you mean that systematic scientific investigation should

allow for the special one-to-one nature of CM treatment. Western

scientists are slowly coming to accept that (Bigler et al, 2003). Yip

et al (2003) conclude that PC-SPES cannot be evaluated by the

same standards established to test synthetic pharmaceutical

compounds. THUS, NEW STANDARDS NEED TO BE

DEVELOPED FOR THE EVALUATION OF HERBAL MEDICINE.

 

Critical scientific research is starting to identify the most important

active ingredients in effective CHM formulae, for example baicalin

and oridonin in PC-SPES. See Hsieh et al (2002) and Marks et al

(2003).

 

PC-SPES got a bad name when it was found to have been

contaminated by DES, indomethacin, warfarin etc. Before then,

many cancer specialists ACCEPTED that it was of great clinical

value. After the scandal broke, some specialists believed that its

clinical effects were due to the CONTAMINANTS, especially DES

(Wadsworth et al, 2003). However, other papers suggest that this

is not the case; the clinical effects of PC-SPES do not depend on

DES (Bonham et al, 2002).

 

Western research will show that herbal formulas are not all

goodness and light, with no side effects. For example, though the

clinical efficacy of PC-SPES in prostate cancer is well accepted

now [in spite of the FDA ban!], its oestrogenic effects have their

negative consequences in men. It is beginning to look that PC-

SPES is a form of phytochemical castration, just as chemical

androgen ablation is (Marks et al, 2003; Raffi et al, 2002; Schiff et

al, 2002).

 

Also, scientists are beginning to realise that the activity of a single

herb cannot account for the overall effects of the effective formula

(Hsieh & Wu, 2002).

 

One of the great benefits of systematic western research on herbs

is that a formula initially used for one condition (for example PC-

SPES in prostate cancer) may be found to have OTHER clinical

uses. For example Huerta et al (2002).al found that PC-SPES is

also effective in colon cancer. Ikezoe et al (2003) found that PC-

SPES also is effective in leukaemia. Sliva et al (2003) found that

Ganoderma (Lingzhi) in PC-SPES inhibits mammary cancer as

well as PC. These are GREAT breakthroughs for herbal medicine in

the west!

 

Here follows a sobering abstract about the current status of

WESTERN approaches to PC:

 

Small EJ, Harris KA. Secondary hormonal manipulation of

prostate cancer. Semin Urol Oncol. 2002 Aug;20(3 Suppl 1):24-30.

Urologic Oncology Program, University of California, San Francisco

Comprehensive Cancer Center, San Francisco, CA 94115, USA.

Prostate cancer is the second leading cause of cancer mortality

among men in Western countries. The initial treatment of advanced

PC is suppression of testicular androgen production by medical or

surgical castration, but nearly all men with metastases will develop

disease progression. Patients with hormone-resistant PC (HRPC)

have a median survival of approximately 18 months, and no therapy

has yet shown a definitive survival advantage. However, in the past

several years, a number of promising new treatment strategies

have emerged. One of the most important new treatment strategies

involves SECONDARY HORMONAL MANIPULATION after the

failure of primary androgen deprivation. This approach is predicated

on the recognition that HRPC is a heterogeneous disease, and

some patients may respond to alternative hormonal interventions

despite the presence of castrate levels of testosterone. Copyright

2002, Elsevier Science (USA). All rights reserved. Publication

Types: Review Review Literature PMID: 12198635 [PubMed -

indexed for MEDLINE]

 

[Phil's comment: Watch this space! For “SECONDARY

HORMONAL MANIPULATION” (above), read: “HORMONAL

MANIPULATION BY CHINESE MEDICINE!”

 

Because of western bigotry, skepticism, prejudice or arrogance,

IMO, Chinese Science alone will NOT be sufficient to put CM " on

the map " in the Western World [i.e. to make it acceptable to

western scientists]. Only WESTERN science, or at least critical

Western confirmation of Chinese findings, will do that.

 

Best regards,

Phil

 

PS: See the other cited references, below.

 

Bigler D, Gulding KM, Dann R, Sheabar FZ, Conaway MR,

Theodorescu D. 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. Oncogene. 2003 Feb 27;22(8):1261-72.

Department of Molecular Physiology and Biological Physics and

Cancer Center, University of Virginia, Health Sciences Center,

Charlottesville, VA 22908, USA. The use of botanical mixtures is

commonplace in patients with PC, yet most of these products have

not been tested rigorously in clinical trials. PC-SPES has been

shown to be effective in clinical trials in patients with PC. Here we

use PC-SPES as a model system to show 'proof of principle' as to

how gene expression profiling coupled with promoter assays can

evaluate the effect of herbal cocktails on human PC. We also show

how such approaches may be used to standardize 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 PC, an

important issue is whether these are the primary drivers of the gene

profile. Our data suggest that gene expression profiles of LNCaP

human PC cells in response to PC-SPES are different from those

found when DES, a synthetic estrogen, is used. This suggests 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 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. 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. PMID: 12606954 [PubMed - indexed for MEDLINE]

 

Bonham M, Arnold H, Montgomery B, Nelson PS. Molecular

effects of the herbal compound PC-SPES: identification of activity

pathways in prostate carcinoma. Cancer Res. 2002 Jul

15;62(14):3920-4. Divisions of Human Biology, Fred Hutchinson

Cancer Research Center, Seattle, Washington 98109, USA.

Clinical trials of the herbal preparation PC-SPES showed

substantial responses in patients with advanced PC. Biochemical

assays and clinical observations suggest that the effects of PC-

SPES are mediated at least in part through estrogenic activity,

although the mechanism(s) remains largely undefined. In this

study, we used cDNA microarray analysis to identify gene

expression changes in LNCaP prostate carcinoma cells exposed

to PC-SPES and estrogenic agents including DES. PC-SPES

altered the expression of 156 genes after 24 h of exposure. Of

particular interest, transcripts encoding cell cycle-regulatory

proteins, alpha- and beta-tubulins, and the androgen receptor were

down-regulated by PC-SPES. A comparison of gene expression

profiles resulting from these treatments indicates that PC-SPES

exhibits activities distinct from those attributable to DES and

suggests that alterations in specific genes involved in modulating

the cell cycle, cell structure, and androgen response may be

responsible for PC-SPES-mediated cytotoxicity. PMID: 12124319

[PubMed - indexed for MEDLINE]

 

 

Hsieh TC, Lu X, Chea J, Wu JM. Prevention and management of

prostate cancer using PC-SPES: a scientific perspective. J Nutr.

2002 Nov;132(11 Suppl):3513S-3517S. Department of Biochemistry

and Molecular Biology, New York Medical College, Valhalla, NY

10595, USA. tze-chen_hsieh Complementary and

alternative therapies are increasingly used in USA by individuals

diagnosed with cancer. PC-SPES is a multiherb dietary

supplement used by many patients with prostate cancer (PC). The

wide acceptance of PC-SPES for hormone-naive and end-stage PC

relates to clinical trials showing significant efficacy and low

toxicity. Although the clinical efficacy of PC-SPES is highly

encouraging, its scientific basis has progressed more slowly. This

article describes our understanding of the in vitro mechanisms of

action of PC-SPES in androgen-dependent LNCaP cells. We first

showed significant suppression of cancer cell growth by restriction

of cell cycle progression at G(1)/S and drastic reductions in the

expression of androgen receptor and PSA by PC-SPES, providing

a mechanistic rationale for its observed clinical effects. Further

investigation of the anti-PC properties of PC-SPES revealed that

two of its multicomponent herbs, Gancao and Huangqin, inhibited

cell growth and down-regulated PSA in a manner comparable with

PC-SPES. Exhaustive characterization of S. baicalensis resulted

in the isolation of baicalein. Here we report that baicalein effectively

suppressed growth and PSA expression and induced G(1)/S arrest

in LNCaP cells. Although baicalein cannot account for the entire

activity of PC-SPES, it does display similar anti-PC activities.

These data suggest that a single herb or bioactive compound could

suffice for PC chemoprevention by effecting multiple changes in

target cells to intervene in PC progression. Further evaluation is

needed of the herbs in PC-SPES and the precise characterization

of their bioactive ingredients. PMID: 12421879 [PubMed - indexed

for MEDLINE]

 

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. 2002 Mar;20(3):583-8.

Department of Biochemistry and Molecular Biology, New York

Medical College, Valhalla, NY 10595, USA. tze-

chen_hsieh PC-SPES is a herbal mixture used as an

alternative treatment by PC patients. Since PC-SPES is derived

from eight individual herbs, each with distinct as well as overlapping

properties, it is of interest to investigate whether a particular herb in

the formulation principally accounts for the biological properties of

PC-SPES. We tested the ability of extracts from individual herbs,

using amounts estimated to be equivalent to that present in the

herbal mixture, to suppress LNCaP cell growth and/or lower PSA

expression, in comparison with cells treated with PC-SPES. Cells

were incubated with 0, 1, and 5 ug/ml of single herbal extract for 72

h and proliferation/viability was measured by trypan blue exclusion.

5 ug/ml ethanol extracts of PC-SPES reduced cell growth of

LNCaP cells by 72-80%, and cell viability decreased similarly. 5

ug/ml of individual herbal extract suppressed cell growth as follows:

Dendranthema morifolium (85% reduction) > Sanqi (81%) >

Gancao (73%) > Donglingcao (71%) > Huangqin (66%) > Lingzhi

(63%) > Banlangen (51%) > Juchizonglan (14%). Only Gancao,

Huangqin and Serenoa repens lowered intracellular and secreted

PSA, while the remaining herbs increased PSA expression. Also,

no uniform response in AR/PSA was observed in individual herb

treated cells, contrary to PC-SPES, which elicited a coordinated

change in AR/PSA. Lack of concordance between changes in

prostate cell growth and prostate specific gene expression makes

it unlikely that the activity of a single herb can account for the

overall effects of PC-SPES. PMID: 11836572 [PubMed - indexed

for MEDLINE]

 

Huerta S, Arteaga JR, Irwin RW, Ikezoe T, Heber D, Koeffler HP.

University of California Los Angeles (UCLA) Center for Human

Nutrition, UCLA School of Medicine, 900 Veteran Avenue, 12-217

Warren Hall, Los Angeles, CA 90095, USA. shuerta

Cancer Res. 2002 Sep 15;62(18):5204-9. PC-SPES inhibits colon

cancer growth in vitro and in vivo. PC-SPES is a mixture of eight

herbs with antiproliferative activity in PC cell lines and antitumor

effects in animal models of PC. In addition, evidence of clinical

efficacy in advanced PC has been reported. PC-SPES has also

been shown to have antitumor activity against several other cancer

cell lines including mammary and neuroepithelial cancer,

melanoma, and leukemia cell lines. Because of these findings, we

investigated the effects of PC-SPES in vitro in colon cancer cell

lines SW480, SW620, and DLD-1 and in vivo in the Apc(min)

mouse, a murine model for intestinal carcinogenesis. For the in

vitro studies, colon cancer cell lines were exposed to an ethanolic

extract of PC-SPES compared with a diluent control [ethanol < or

= 0.3% (v/v)]. PC-SPES resulted in a marked suppression of cell

proliferation in all colon cancer cells studied. PC-SPES (3 micro

l/ml) caused a 95% inhibition of cell proliferation of the DLD-1 colon

cancer cell line, and similar results were observed in the SW480

and SW620 colon cancer cell lines. Cell cycle analysis showed a

drastic (> or =60%) accumulation of cells in the G(2)-M phase with

a concomitant decrease of cells in the G(0)-G(1) phase in all colon

cancer cell lines studied after treatment with PC-SPES (1.5 micro

l/ml for 48 h). Western blot analysis showed a decrease in protein

levels of beta-tubulin in the SW620 cell line exposed to PC-SPES.

Terminal deoxynucleotidyl transferase-mediated nick end labeling

analysis revealed an increase in apoptotic colon cancer cells

incubated with PC-SPES. For the in vivo studies, female 4-5-week-

old Apc(min) mice were randomized to two groups: a PC-SPES-

treated group (n = 11) received 250 mg/kg/day (0.2 ml) PC-SPES

via gastrointestinal gavage; and a control group (n = 10) received

0.2 ml of the vehicle solution (1.5% carboxymethylcellulose with

0.2% Tween 20) via gastrointestinal gavage. Both groups were

treated five times a week for 10 weeks. After treatment, the

gastrointestinal tract was dissected for polyp scoring by two

observers blinded to treatment. The Apc(min) mice given PC-SPES

had a 58% reduction in tumor number and a 56% decrease in

tumor load. No effect on either food intake or body weight was

observed in the treated versus sham groups. The present study is

the first to report the potent activity of PC-SPES against colon

cancer. Both cell cycle arrest and apoptosis occurred after

treatment with PC-SPES. This suggests that the components of

this herbal mixture, either independently or in combination, acted in

colon cancer, resulting in a drastic effect on tumor initiation and

tumor progression. PMID: 12234985 [PubMed - indexed for

MEDLINE]

 

Ikezoe T, Chen S, Saito T, Asou H, Kyo T, Tanosaki S, Heber D,

Taguchi H, Koeffler HP. Department of Medicine, Kochi Medical

School, Nankoku, Kochi 783-8505, Japan. ikezoet-

ms.ac.jp Int J Oncol. 2003 Oct;23(4):1203-11. PC-SPES

decreases proliferation and induces differentiation and apoptosis of

human acute myeloid leukemia cells. PC-SPES has been shown

to be active against PC cells in vitro as well as in patients. In this

study, we discovered that it has anti-leukemia activity. HL-60, NB4,

U937 and THP-1 human acute myeloid leukemia cells were

cultured in the presence of various concentrations of PC-SPES

(0.06-0.5 micro l/ml) for 4 days, and cell numbers were counted by

Trypan blue exclusion. PC-SPES inhibited proliferation of these

cells with an ED50 of 0.17, 0.09, 0.18, 0.32 micro l/ml,

respectively. In clonogenic assay, PC-SPES inhibited growth of HL-

60 cells (ED50, 0.043 micro l/ml). On the other hand, PC-SPES

(0.1 micro l/ml) stimulated growth of normal myeloid committed

stem cells (CFU-GM) by 1.4-fold of control (p=0.03). Anti-leukemia

effects also occurred against freshly isolated leukemia cells from

acute myeloid leukemia (AML) and myelodysplastic syndrome

(MDS) patients. Interestingly, when PC-SPES was combined with

ATRA, the antiproliferative effect was markedly enhanced. For

example, PC-SPES (0.125 micro l/ml) or ATRA (10(-8) mol/l)

inhibited growth of HL-60 cells after 4 days of culture, by

approximately 40 and 30%, respectively; simultaneous treatment

with both, suppressed growth by 80%. In addition, PC-SPES

induced differentiation of HL-60 and NB4 cells, as measured by

expression of CD11b and reduction of NBT. ATRA synergistically

enhanced this activity. For example, either PC-SPES (0.5 micro

l/ml) or ATRA (10(-8) mol/l) induced 23 and 18% of HL-60 cells,

respectively to express CD11b on day 2 of culture; and when both

were combined, 60% of HL-60 cells were stimulated to express

CD11b antigen. Furthermore, PC-SPES (0.5 micro l/ml) produced

apoptosis of HL-60 and NB4 cells, as measured by TUNEL assay,

with 17% of HL-60 cells and 52% of NB4 cells becoming apoptotic

on their third day of culture. Importantly, PC-SPES stimulated

expression of the novel myeloid specific transcription factor

C/EBPepsilon in HL-60 and NB4 cells. Taken together, PC-SPES

inhibits growth and induces differentiation and apoptosis of myeloid

leukemia cells, and enhances the antiproliferative and

prodifferentiative effects of ATRA on these cells. PC-SPES might

be useful with ATRA to treat patients with acute promyelocytic

leukemia (APL), and it could have a role in other types of cancers

including MDS. PMID: 12964005 [PubMed - in process]

 

 

Marks LS, DiPaola RS, Nelson P, Chen S, Heber D, Belldegrun

AS, Lowe FC, Fan J, Leaders FE Jr, Pantuck AJ, Tyler VE. PC-

SPES: herbal formulation for prostate cancer. Urology. 2002

Sep;60(3):369-75; discussion 376-7. Comment in: Urology. 2003

Jun;61(6):1292. Urological Sciences Research Foundation, Culver

City, California 90232, USA. PC-SPES is a potent eight-herb

formulation sold directly to consumers; it has promising efficacy to

treat PC. The product induces a castrate status in most, if not all,

men, resulting in a 50% or greater PSA reduction in the great

majority of men with androgen-dependent PC and in >50% of the

men with androgen-independent PC. The duration of response is

not yet clear. The efficacy of PC-SPES appears to exceed that of

androgen ablation alone, but is not necessarily separate from an

estrogenic effect. Common side effects include gynecomastia,

nipple tenderness, loss of libido, and impotency; uncommon side

effects include a 4% incidence of thromboembolic phenomena, but

also two reports of bleeding diatheses. The mechanisms of action

may involve downregulation of the androgen receptor, induction of

apoptosis by way of inhibition of the bcl-2 gene, and increased

expression of p53. Two marker compounds in PC-SPES are

baicalin and oridonin, both of which exhibit antiproliferative effects

in PC cell lines. Thousands of men are using this nonprescription

medicine, and physicians should ask patients specifically about its

use. PC-SPES is of great interest in men with androgen-

independent PC, an area in which future research should be

primarily directed. Publication Types: Review Review, Tutorial

PMID: 12350462 [PubMed - indexed for MEDLINE]

 

Rafi MM, Vastano BC, Zhu N, Ho CT, Ghai G, Rosen RT, Gallo

MA, DiPaola RS. Novel polyphenol molecule isolated from licorice

root (Glycrrhiza glabra) induces apoptosis, G2/M cell cycle arrest,

and Bcl-2 phosphorylation in tumor cell lines. J Agric Food Chem.

2002 Feb 13;50(4):677-84. Department of Food Science and Center

for Advanced Food Technology, Rutgers University, 65 Dudley

Road, New Brunswick, New Jersey 08901-8520, USA. Herbal

therapies are commonly used by patients with cancer, despite little

understanding about biologically active chemical derivatives. We

recently showed that PC-SPES, which contains Gancao, had anti-

PC activity attributable to estrogen(s) that produced a chemical

castration. A recent study also showed that Gancao alone

decreased circulating testosterone in men. Other studies showed

PC-SPES antitumor activity in vitro associated with decreased

expression of anti-apoptotic protein Bcl-2 and in patients

independent of chemical castration. This suggests that other

mechanisms of antitumor activity exist separate from chemical

castration. In the present study, we assessed Gancao extract for

effects on Bcl-2 to identify novel cytotoxic derivatives. Gancao

extract induced Bcl-2 phosphorylation as shown by immunoblot

and G2/M cell cycle arrest, similarly to clinically used

antimicrotubule agents such as paclitaxel. Bioassay-directed

fractionations resulted in a biologically active fraction for Bcl-2

phosphorylation. HPLC separation followed by mass spectrometry

and NMR identified 6 compounds. Only one molecule was

responsible for Bcl-2 phosphorylation; it was identified as 1-(2,4-

dihydroxyphenyl)-3-hydroxy-3-(4'-hydroxyphenyl) 1-propanone (beta-

hydroxy-DHP). The effect on Bcl-2 was structure specific, because

alpha-hydroxy-DHP, 1-(2,4-dihydroxyphenyl)-2-hydroxy-3-(4'-

hydroxyphenyl) 1-propanone, in contrast to beta-hydroxy-DHP, was

not capable of Bcl-2 phosphorylation. Pure beta-hydroxy-DHP

induced Bcl-2 phosphorylation in mammary and prostate tumor

cells, G2/M cell cycle arrest, apoptosis shown by Annexin V and

TUNEL assay, decreased cell viability shown by a tetrazolium

(MTT) assay, and altered microtubule structure. Gancao contains

beta-hydroxy-DHP, which induced Bcl-2 phosphorylation,

apoptosis, and G2/M cell cycle arrest, in mammary and prostate

tumor cells, similarly to the action of more complex (MW >800)

antimicrotubule agents used clinically. PMID: 11829627 [PubMed -

indexed for MEDLINE]

 

Schiff JD, Ziecheck WS, Choi B. Pulmonary embolus related to

PC-SPES use in a patient with PSA recurrence after radical

prostatectomy. Urology. 2002 Mar;59(3):444. James Buchanan

Brady Department of Urology, New-York Presbyterian Hospital,

Cornell Medical Center, New York, New York, USA. Patients

diagnosed with a rising PSA level after radical prostatectomy

represent a therapeutic dilemma. Herbal therapies including PC-

SPES have gained popularity as alternatives to conventional

hormonal ablation in such patients as a result of the perceived

benefits of using natural products and proven clinical response in

decreasing PSA levels. PC-SPES is one of the most popular herbs

with known estrogenic activity in vitro and in vivo. Estrogenic

compounds increase the risk of thromboembolic events. However,

no specific guidelines are available with regard to the risk of

thromboembolic events for patients using PC-SPES. We report a

case of a patient treated with PC-SPES for PSA recurrence after

radical prostatectomy who presented with pulmonary embolus and

a right common femoral deep venous thrombus. PMID: 11880092

[PubMed - indexed for MEDLINE]

 

 

Sliva D, Sedlak M, Slivova V, Valachovicova T, Lloyd FP Jr, Ho

NW. Biologic activity of spores and dried powder from Ganoderma

lucidum for the inhibition of highly invasive human Breast and

prostate cancer cells. J Altern Complement Med. 2003

Aug;9(4):491-7. Cancer Research Laboratory, Methodist Research

Institute, Clarian Health Partners Inc., Indianapolis, IN 46202, USA.

dsliva OBJECTIVE: Lingzhi (Jap: Reishi) has been

used in East Asia as a home remedy to prevent or cure cancer.

Furthermore, Lingzhi is one of the herbs in the herbal mixture PC-

SPES that has become an alternative herbal therapy for PC.

Because the dried powder of Lingzhi is commercially available as a

dietary supplement itself, the purpose of this study was to evaluate

the biologic activity of samples of Lingzhi from different sources.

METHODS: Samples of Lingzhi were characterized

morphologically and evaluated for their ability to inhibit cell

migration of highly invasive mammary cancer MDA-MB-231 cells

and PC PC-3 cells. Because the inhibition of cell motility is directly

linked to the inhibition of the signaling pathway for constitutively

active NF-kappaB in mammary and PC cells, we determined how

different samples of Lingzhi inhibit constitutively active NF-kappaB

in a reporter gene assay. RESULTS: Some samples of Lingzhi

strongly inhibited cancer cell migration comparable to the inhibition

of constitutively active NF-kappaB, whereas other samples showed

less or no activity in highly invasive estrogen receptor-negative

mammary cancer cells or androgen receptor-negative PC cells,

respectively. Interestingly, we did not find any correlation between

the purity and composition (spores versus powder) of Lingzhi and

biologic activity. CONCLUSIONS: Lingzhi had strong activity

against mammary and PC cells. Nevertheless, the composition of

samples did not correlate with their ability to inhibit cell migration

and activation of NF-kappaB in vitro. PMID: 14499024 [PubMed - in

process]

 

Thomson JO, Dzubak P, Hajduch M.. Prostate cancer and the food

supplement, PC-SPES. Minireview. Neoplasma. 2002;49(2):69-74.

Department of Pediatrics, Faculty of Medicine, Palacky University

and Faculty Hospital in Olomouc, Czech Republic Cancer of the

prostate has now become the most frequently diagnosed cancer in

males in America and its incidence has increased in many

westernised countries. Surgery, radiotherapy and androgen

ablation form the mainstay of its treatment. However, these

treatment modalities are ineffective in a large percentage of

patients due to grade of tumor at presentation, sensitivity to

radiotherapy, hormone-insensitive profile of tumor cell population,

etc. Because of the woeful ineffectiveness of these standard

treatment modalities on the overall survival rate from PC in the past

50 years, a more radical approach to the treatment of this cancer

is justified. To this end some of the latest innovative approaches

are now being tested as tools in PC research, including those

pioneered in molecular and cellular biology and immunology. There

has also arisen a considerable interest in the modification of diet

and the use of herbs and a great interest has been stimulated in

PC-SPES, a herbal food supplement sold in the USA. This

product, which is composed of eight herbs, is recommended as a

food supplement for those suffering from PC and there are many

anecdotal, scientific and clinical claims for its efficacy. This is a

review of some of the in vivo and in vitro research carried out on this

product. Publication Types: Review Review, Tutorial PMID:

12088108 [PubMed - indexed for MEDLINE]

 

Wadsworth T, Poonyagariyagorn H, Sullivan E, Koop D, Roselli

CE. In vivo effect of PC-SPES on prostate growth and hepatic

CYP3A expression in rats. J Pharmacol Exp Ther. 2003

Jul;306(1):187-94. Epub 2003 Apr 03. Department of Physiology

and Pharmacology L334, Oregon Health and Science University,

3181 SW Sam Jackson Park Rd., Portland, OR 97239-3098, USA.

PC-SPES, a proprietary mixture composed of eight different herbs,

is used worldwide as an alternative treatment by PC patients. It

has been suggested that the clinical and in vitro antitumor activity

exhibited by PC-SPES may be due to estrogenic activity, which in

turn may be mediated by the presence of undeclared prescription

drug contaminants. Here, we evaluated the in vivo effects of two

different commercial lots of PC-SPES in male and female rats. Our

high-pressure liquid chromatography analysis coupled with gas

chromatography/mass spectrometry analysis by an independent

laboratory suggested that PC-SPES lot 5430125 was

contaminated with DES, whereas lot 5431249 was not. Treatment

of male rats with PC-SPES lot 5430125 or DES alone reduced the

weight of androgen target organs and decreased circulating levels

of sex steroids and LH, whereas lot 5431249 was without effect.

Also, lot 5430125 and DES, but not lot 5431249 increased uterine

weight in female rats. These results suggest that the inhibitory

effects on androgen targets are mediated through suppression of

the hypothalamic-pituitary axis and this suppression is probably

due to DES contamination. We assessed the effects of both lots of

PC-SPES and DES on hepatic cytochrome P450 expression and

activity. Both lots of PC-SPES and DES reduced CYP3A activity

and protein levels. Because the response of CYP3A to PC-SPES

was not dependent on whether it contained DES, a phytochemical

component of PC-SPES is most likely responsible for this effect.

Inhibition of CYP3A has important implications for potential herbal-

drug interactions. PMID: 12676889 [PubMed - indexed for

MEDLINE]

 

Yip I, Cudiamat M, Chim D. PC-SPES for treatment of prostate

cancer: herbal medicine. Curr Urol Rep. 2003 Jun;4(3):253-7.

Department of Medicine, David Geffen School of Medicine,

University of California, Los Angeles, 100 UCLA Medical Plaza,

Suite 522, Los Angeles, CA 90024, USA. iyip

The number of patients who seek treatment with complementary

and alternative medicine has increased during the past decade.

The trend is primarily driven by consumers who start to change

their views toward conventional pharmaceutical approaches that are

offered to them. Among all complementary and alternative

therapies used in the management of PC, Prostate Cancer-SPES

(PC-SPES) has attracted much national attention because of its

potency, controversy, and recall by the US Food and Drug

Administration. PC-SPES contains extracts from a mixture of eight

common herbs that have been used for thousands of years. This

article is devoted to reviewing the basic and clinical data of using

PC-SPES in PC therapy. It also explores the difference in

philosophies between Western medicine and herbal medicine and

explains the inherent difficulties in evaluating herbal medicine. The

article concludes that PC-SPES cannot be evaluated by the same

standards established to test synthetic pharmaceutical

compounds. Thus, new standards need to be developed for the

evaluation of herbal medicine. Publication Types: Review Review,

Tutorial PMID: 12756091 [PubMed - indexed for MEDLINE]

 

 

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