Category Archives: Leukemia

Induction of cell cycle changes and modulation of apoptogenic/anti-apoptotic and extracellular signaling regulatory protein expression by water extracts of I’m-Yunity (PSP).

Hsieh TC, Wu P, Park S, Wu JM.

Department of Biochemistry & Molecular Biology, New York Medical College, Valhalla, NY 10595, USA. Tze-Chen_Hsieh@nymc.edu

Abstract

BACKGROUND: I’m-Yunity (PSP) is a mushroom extract derived from deep-layer cultivated mycelia of the patented Cov-1 strain of Coriolus versicolor (CV), which contains as its main bioactive ingredient a family of polysaccharo-peptide with heterogeneous charge properties and molecular sizes. I’m-Yunity (PSP) is used as a dietary supplement by cancer patients and by individuals diagnosed with various chronic diseases. Laboratory studies have shown that I’m-Yunity (PSP) enhances immune functions and also modulates cellular responses to external challenges. Recently, I’m-Yunity (PSP) was also reported to exert potent anti-tumorigenic effects, evident by suppression of cell proliferation and induction of apoptosis in malignant cells. We investigate the mechanisms by which I’m-Yunity (PSP) elicits these effects.

METHODS: Human leukemia HL-60 and U-937 cells were incubated with increasing doses of aqueous extracts of I’m-Yunity (PSP). Control and treated cells were harvested at various times and analyzed for changes in: (1) cell proliferation and viability, (2) cell cycle phase transition, (3) induction of apoptosis, (4) expression of cell cycle, apoptogenic/anti-apoptotic, and extracellular regulatory proteins.

RESULTS: Aqueous extracts of I’m-Yunity (PSP) inhibited cell proliferation and induced apoptosis in HL-60 and U-937 cells, accompanied by a cell type-dependent disruption of the G1/S and G2/M phases of cell cycle progression. A more pronounced growth suppression was observed in treated HL-60 cells, which was correlated with time- and dose-dependent down regulation of the retinoblastoma protein Rb, diminution in the expression of anti-apoptotic proteins bcl-2 and survivin, increase in apoptogenic proteins bax and cytochrome c, and cleavage of poly(ADP-ribose) polymerase (PARP) from its native 112-kDa form to the 89-kDa truncated product. Moreover, I’m-Yunity (PSP)-treated HL-60 cells also showed a substantial decrease in p65 and to a lesser degree p50 forms of transcription factor NF-kappaB, which was accompanied by a reduction in the expression of cyclooxygenase 2 (COX2). I’m-Yunity (PSP) also elicited an increase in STAT1 (signal transducer and activator of transcription) and correspondingly, decrease in the expression of activated form of ERK (extracellular signal-regulated kinase).

CONCLUSION: Aqueous extracts of I’m-Yunity (PSP) induces cell cycle arrest and alterations in the expression of apoptogenic/anti-apoptotic and extracellular signaling regulatory proteins in human leukemia cells, the net result being suppression of proliferation and increase in apoptosis. These findings may contribute to the reported clinical and overall health effects of I’m-Yunity (PSP).

PMID: 16965632 [PubMed – indexed for MEDLINE]PMCID: PMC1574346Free PMC Article

http://www.ncbi.nlm.nih.gov/pubmed/16965632

Polysaccharopeptide enhances the anticancer activity of doxorubicin and etoposide on human breast cancer cells ZR-75-30.

Wan JM, Sit WH, Louie JC.

Food and Nutritional Science Division, School of Biological Sciences, The University of Hong Kong, Hong Kong SAR, PR China. jmfwan@hkusua.hku.hk

Abstract

In search of natural bioactive microbial compounds with adjuvant properties, we have previously showed that the polysaccharopeptide (PSP), isolated from Chinese medicinal mushroom Coriolus versicolor, was able to enhance the cytotoxicity of certain S-phase targeted-drugs on human leukemic HL-60 cells via some cell-cycle and apoptotic-dependent pathways. The present study aimed to investigate whether the synergism of mechanisms of PSP with certain chemotherapeutic drugs also applies to human breast cancer. PSP treatment enhanced the cytotoxicity of doxorubicin (Doxo), etoposide (VP-16) but not cytarabine (Ara-C). Bivariate bromodeoxyuridine (BrdUrd)/DNA flow cytometry analysis estimated a longer DNA synthesis time (Ts) for the PSP treated cancerous cells suggesting that PSP enhanced the apoptotic effect of Doxo and VP-16 via creating an S-phase trap in the human breast cancer cell line ZR-75-30. The participation of PSP in the apoptotic machinery of the chemotherapeutic agents was further supported by a reduced ratio of protein expression of Bcl-xL/Bax of the cancer cells. This study provides further insight into the synergistic mechanisms of PSP and supports the hypothesis that the anticancer potentials of PSP is not limited to leukemia but may also be used as an adjuvant therapy for breast cancers.

PMID: 18292947 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/18292947

Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT) on human leukemia HL-60 cells.

Wan JM, Sit WH, Yang X, Jiang P, Wong LL.

Agricultural, Food and Nutritional Sciences Division, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China. jmfwan@hkusua.hku.hk.

Abstract

ABSTRACT:

BACKGROUND: Polysaccharopeptide (PSP) from Coriolus versicolor (Yunzhi) is used as a supplementary cancer treatment in Asia. The present study aims to investigate whether PSP pre-treatment can increase the response of the human leukemia HL-60 cells to apoptosis induction by Camptothecin (CPT).

METHODS: We used bivariate bromodeoxyuridine/propidium iodide (BrdUrd/PI) flow cytometry analysis to measure the relative movement (RM) of the BrdUrd positively labeled cells and DNA synthesis time (Ts) on the HL-60 cell line. We used annexin V/PI flow cytometry analysis to quantify the viable, necrotic and apoptotic cells. The expression of cyclin E and cyclin B1 was determined with annexin V/PI flow cytometry and western blotting. Human peripheral blood mononuclear cells were used to test the cytotoxicity of PSP and CPT.

RESULTS: PSP reduced cellular proliferation; inhibited cells progression through both S and G2 phase, reduced 3H-thymidine uptake and prolonged DNA synthesis time (Ts) in HL-60 cells. PSP-pretreated cells enhanced the cytotoxicity of CPT. The sensitivity of cells to the cytotoxic effects of CPT was seen to be the highest in the S-phase and to a small extent of the G2 phase of the cell cycle. On the other hand, no cell death (measured by annexin V/PI) was evident with the normal human peripheral blood mononuclear cells with treatment of either PSP or CPT.

CONCLUSION: The present study shows that PSP increases the sensitization of the HL-60 cells to undergo effective apoptotic cell death induced by CPT. The pattern of sensitivity of cancer cells is similar to that of HL-60 cells. PSP rapidly arrests and/or kills cells in S-phase and did not interfere with the anticancer action of CPT. PSP is a potential adjuvant to treat human leukemia as rapidly proliferating tumors is characterized by a high proportion of S-phase cells.

PMID: 20423495 [PubMed – in process]PMCID: PMC2874562

http://www.ncbi.nlm.nih.gov/pubmed/20423495

Activation of human natural killer cells by the protein-bound polysaccharide PSK

The protein-bound polysaccharide PSK was tested for the ability to activate human natural killer (NK) cells. When blood lymphocytes and purified CD3-CD16 ÷ large granular lymphocytes (LGL) were treated in vitro overnight with PSK, they demonstrated enhanced NK cell activity against K562. The PSK-activated killer cells also lysed NK-resistant targets and freshly isolated autologous and allogeneic tumor cells. The PSK effect was observed with concentrations that could be obtained in the blood of cancer patients receiving oral administration of PSK. PSK-induced enhancement of NK activity was not abrogated by monoclonal antibodies (mAb) that neutralized interferon (IFN)o~, IFN3,, or interleukin-2 (IL-2). In addition, mAb reactive with p55 (~ chain) or p75 (/3 chain) glycoproteins of IL-2 receptors had no effects on PSK-enhanced NK activity even when used simultaneously. These results indicate that the PSK could activate human NK cells independently of IFN and IL-2/IL-2R systems.

For full article click here.

A Review of Research on the Protein-Bound Polysaccharide from the Mushroom Coriolus Versicolor

Mushrooms are known for their nutritional and medicinal value (Breene, 1990) and also for the diversity of bioactive compounds they contain. The mushroom Coriolus versicolor (Yun Zhi) was recorded in the Compendium of Materia Medica by Li Shi Zhen during the Ming Dynasty in China, as being beneficial to health and able to bring longevity if consumed regularly. Various products derived from this mushroom and claimed to have medicinal value are commercially available. Among them, PSK (Sakagami et al., 1991) and PSP are the most prominent. It is the intent of this article to summarize research data pertaining to PSP.

PSK (Sakagami et al., 1991) and PSP are two chemically related products of the mushroom Coriolus versico~or isolated from deeplayer cultivated mycelia of the COV-1 and CM-101 strains, by Chinese and Japanese investigators, respectively. The similarities and differences of the two products have been pointed out by the Fungi Research Institute (1993a). Both possess a molecular weight of approximately 100 kDa and their polypeptide moieties are rich in aspartic acid and glutamic acid. Monosaccharides with o~-1,4 and [3-1,3 glucosidic linkages constitute the pol~saccharide moieties of PSP and PSK: fucose is found in the latter¢ whereas arabinose and rhamnose occur in the former. Both PSP and PSK have been found to be immunoenhancing and effective against tumor cells.

For full article click here.

PSP Coriolus Extract – How It Works (Mechanism Of Action) – MD Anderson, Texas

The multiple and complex mechanisms of action of Coriolus Versicolor PSP have been demonstrated through in vitro and animal studies. Coriolus PSP has suppressed the growth of human cancer cell lines in mice (sarcoma 180, lung adenocarcinoma and Lewis lung cancer).

It has also inhibited incorporation of two structural units of DNA (uridine and thymidine) in Ehrlich ascites tumor cells, inhibited the growth of P388 leukemia cells, and demonstrated anti-proliferative activity against cell lines of human gastric cancer, lung cancer, lymphoma, and mononuclear leukemia.

Coriolus PSP has reversed tumor-induced immunodeficiencies in sarcoma-bearing mice by increasing immunoglobulin G and C3 complement levels9. It has also been associated with increases in white blood cell count, serum IgG, CD4, CD8, B-lymphocytes, and neutrophils, along with a higher survival rate of tumor bearing mice3. Many of these effects have been attributed to PSP being a strong scavenger of superoxide and hydroxyl radicals. Coriolus Versicolor PSP has also been found to restrict the cell cycle of HL-60 leukemic cells through apoptosis.
These and other immune effects of PSK and PSP are described in reviews by Fisher and Yang, Ooi and Liu and Chu, Ho and Chow.

Source: (mdanderson.org)

Coriolus Versicolor – The Miracle Mushroom

This extract taken from quantumhealing.co.za details various trials and treatments of Coriolus Veriscola.

It shrank his liver tumor by 90%––after his doctor gave up on him.

A man describes his oncologist as “the most negative man I ever met.” The doctor treated Mr. G. for liver cancer for six years, then gave him up as untreatable. “After the chemo failed, he threw up his hands, shrugged his shoulders, wished me good luck, and said there was nothing else he could do,” according to Mr. G. “And surgery couldn’t be performed either, because the consulting surgeon saw that the tumor was wrapped around my vena cava blood vessel.”

Mr G. told his oncologist, “I totally reject what you are telling me. I do not accept that nothing can be done to affect the outcome of this disease.” The doctor said, “Well, I know what I’m talking about when it comes to cancer. I’m a scientist.”

Mr G. shot back, “Yes, but you’re not God!” Four years later the patient was healthy again after using the type of therapies known as CAIM (complementary/ alternative/integrative medicine), especially including capsules containing the powdered extract of a mushroom, Coriolus versicolor. Mr G. learned about the remedy on the Internet and he can tell you all about it, having downloaded nearly 400 studies.

Amazingly, Mr. G.’s liver cancer reduced to less than ten percent of its original size. His CEA (carcinoembryonic antigen) cancer marker fell more than two-thirds from 296 to 97.9.

What is Coriolus Versicolor?

Like all mushrooms, Coriolus versicolor is a fungus, one of more than a half million varieties worldwide. Many of them have been known for thousands of years to have medicinal properties. And as you may know, gourmets the world over prize both wild and commercially grown mushrooms. Some European cookbooks even call them “flowers of the fall.” Whatever you call them, certain mushrooms are a perfect food for staying trim and healthy. They have little or no fat and some species, like Coriolusversicolor, boast valuable therapeutic and nutritional benefits. But a few fungi are poisonous and we do not recommend that nonexperts attempt to harvest their own. Coriolus versicolor goes by a number of botanical names, including Trametes versicolor and Boletus versicolor.

“Versicolor” refers to the mushroom’s various colors. In North America, the common name is “turkey tail,” while in Japan it is called by a name meaning “mushroom by the river bank” and in China its name indicates it’s a cloud fungus that grows best in the rain.

Over 400 clinical studies have shown that a purified extract derived from the mushroom Coriolus versicolor offers strong benefits for the immune system. Clinical studies indicate the extract’s ingredients are especially effective against stomach, uterine, colon and lung cancer.

Anecdotal evidence and clinical experience suggest it also works well against prostate, breast, liver and colorectal  cancer. Studies of rats and mice show that this mushroom is effective against many experimental animal cancers such as sarcoma and hepatoma.

Martha I.’s lung cancers disappear

“Of course,” says Dr. Bailey, “some cancer patients take Coriolus versicolor even while they engage in radiation treatment or chemotherapy. Or the patients don’t submit to chemotherapy or radiotherapy at all but rely, instead, exclusively on nutritional therapies with the medicinal mushroom as the main treatment ingredient.

“For example, one of my patients, Martha I., a 34-year-old woman working in the health field, consulted me with a cancer spreading at two sites in her lungs. Orthodox treatment had been tried but no longer was effective. She discontinued her smoking of two cigarette packs a day and embarked on nutritional therapies.

The nutrients included Martha’s completing six months of taking Coriolus versicolor. After this halfyear, radiological examination showed that all of her lung tumors had disappeared. Seeing her current progress, orthodox medicine probably would declare this patient to be cured.”

Blood tests show how the mushroom boosts immunity

I spoke with a doctor who measures natural killer cell (NK) counts and considers them a valuable cancer

marker. Kenneth Bock, M.D., is the medical director of two holistic medical clinics, one in Rhinebeck, New York and the other in Albany. “Because it increases natural killer (NK) cell activity, I think of using Coriolus versicolor mainly when I’m confronted with a patient suffering from cancer or a viral infection,” he says. “This mushroom is one of the main medicinal compounds I use to boost a diminished blood reading which records NK activity. The mushroom’s active biological response modifier produces a marked improvement in NK cell function and number, something I monitor by blood testing. If the blood reading is low, my patient takes greater amounts of PSK capsules. And, although it’s an expensive and sophisticated assay, I repeat my NK cell testing inside of a month or two. In a number of patients, I’ve seen some nice blood test improvement.”

Dr. Bock finds that a few patients with advanced metastatic cancer see their NK counts jump from 2 or 3 to a normal 20 to 50.

Patient’s immune system recovers

“I can illustrate what I’m saying by providing a before-and-after case history plus the literature that backs my claim,” Dr. Bock states. His patient was a white, married computer consultant named Marty E., sixty years old and suffering from high blood pressure and arteriosclerosis when he was also found to have polyps on his larynx. These were removed, with radiation therapy as a follow-up. But then Marty E. was also found to have prostate cancer.

“His blood test showed diminished natural killer cell activity at the level of 6 m/u,” Dr. Bock states. “Still, Marty wanted no conventional therapy for prostate cancer. So I started him on alternative medical therapies for prostate cancer and to improve his deficient NK cell activity. Coriolus versicolor was a definite part of his treatment regimen.

“Within two months, the patient’s NK cell activity elevated to 18 m/u. And two months after that his NK cell activity increased to a normal 31 m/u. Now the man is doing well physically, and he tells me he feels great! I would say this type of response to the  PSK therapy is usual; the patient’s quality of life does improve dramatically and he or she feels asense of well-being,” according to Dr. Bock.

A naturpathic doctor named Tori Hudson told of her clinical experience using PSK for breast cancer patients during and after chemotherapy. “My impression is that patients taking Coriolus versicolor are experiencing less side effects from chemotherapy such as diminished fatigue, less nausea (but not less hair loss), and more stable white blood cell counts. I have not measured natural killer cell counts,” she states.

Animal studies confirm what patients see for themselves

Animal studies show PSK is effective against a long list of cancers including melanoma, sarcoma, mammary cancer, colon cancer and lung cancer. Studies also show it inhibits metastasis to other sites. The studies indicate PSK enhances the immune system and battles cancer cells. It’s been shown to prolong the survival time and stimulate the production of cancer antibodies in mice with cancer.

PSK is also a potent antiviral remedy that may hold new hope for HIV-AIDS. It even lowers cholesterol in animals and speeds up recovery from burns in rabbits when used in combination with the herb Astragalus membranaceus.

Can be used in combination with conventional treatments

Human patients who have decided to stick with conventional chemotherapy and radiation therapy need to know that PSK renders these toxic treatments much more effective, as shown by a number of clinical studies.

A Japanese study looked at the effectiveness of 200 phytochemicals (plant substances) when used in combination with chemotherapy and radiation. Coriolus versicolor was found to be the best of the bunch. The researchers suggest that this medicinal mushroom seems to protect the immune system from being suppressed by prolonged use of chemotherapy drugsand by the cancer itself.

Further investigations indicate a marked improvement in the survival rates of chemo and radiationpatients taking the mushroom therapy when compared with those who did not. For patients with Stage I lung cancer observed over ten years, the tumor shrinkage and survival rate was 39 percent for those taking PSK compared to only 16 percent for patients receiving the toxic therapies without the mushroom extract. That’s a huge difference––more than twice as many survived and/or improved with the help of PSK.

Those lung cancer patients with more serious Stage II cancer experienced a 22 percent tumor shrinkage and survival rate over ten years when they took Coriolus versicolor orally while being treated with chemo or radiation. Among the people who didn’t take the herbal remedy the figure was a mere five percent.

From this study of 185 lung cancer patients it appears the mushroom extract can make the toxic therapies anywhere from two to four times more effective.

A Japanese study of 262 gastric cancer patients tested the mushroom’s efficacy following surgery. During a follow-up period ranging from five to seven years, the half who received the mushroom extract survived at substantially higher rates. The researchers concluded that PSK was a useful adjunctive therapy to surgery and chemo.

A Japanese study of breast cancer patients found similar results: Those who received PSK along with chemotherapy had better outcomes than those who did not. And a study of 28 patients suffering from acute leukemia––all on chemotherapy––showed an average survival time of 21 months for those who took the mushroom extract and 12 months for those who did not.