Category Archives: Cancer

Cancer, Medical Studies, PSP

The cell death process of the anticancer agent polysaccharidepeptide (PSP) in human promyelocytic leukemic HL-60 cells.

Yang X, Sit WH, Chan DK, Wan JM.

Department of Zoology, The University of Hong Kong, Pokfalum Road, Hong Kong, SAR, P.R. China.

Abstract

The polysaccharide peptide (PSP) isolated from the mycelia of Chinese Medicinal fungus Coriolus versicolor has proven

benefits in clinical trials in China but the mechanism of action has not been elucidated. In this study, HL-60 cell line was

used to investigate the anti-proliferation and cell death process of PSP. The cytotoxicity of PSP on normal human

T-lymphocytes was also evaluated. We show that PSP induced apoptosis of human promyelocytic leukemia HL-60 cells

but not of normal human T-lymphocytes. The apoptotic machinery induced by PSP was associated with a decrease in

Bcl-2/Bax ratio, drop in mitochondrial transmembrane potential, cytochrome c release, and activation of caspase-3, -8 and

-9. Activation of the cellular apoptotic program is a current strategy for the treatment of human cancer, and the selectivity

of PSP to induce apoptosis in cancerous and not on normal cells supports its development as a novel anticancer agent.

PMID: 15870943 [PubMed – indexed for MEDLINE]

PubMed

U.S. National Library of Medicine

National Institutes of Health

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Cancer, in vitro, Medical Studies, PSK, Tumor

Suppression of cancer cell growth in vitro by the protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) with SOD mimicking activity.

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Cancer Biother. 1994 Spring;9(1):63-9.

Kobayashi Y, Kariya K, Saigenji K, Nakamura K.

Molecular Biology Laboratory, Kotasato University School of Medicine, Kanagawa, Japan.

Abstract

The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses the mimicking activity of superoxide

dismutase (SOD). Examination was made of the suppressive effects of PS-K on cancer cell lines cultured in vitro. The

SOD activity of LLC-WRC-256 (Walker 256 fibrosarcoma) cell lines was less than that of NRK-49F (rat normal kidney

fibroblast), H4-II-E (rat hepatoma) and H4-II-E-C3 (rat hepatoma) cell lines. This activity in Walker 256 fibrosarcoma cells

increased by 3.6 times and H2O2 concentration, by 2.56 times by PS-K 500 micrograms/ml. Cell proliferation was

consequently suppressed and living cells decreased to less than 50% of the cells cultured without PS-K. Catalase and

glutathione peroxidase activity changed little by PS-K. The sensitivity of cancer cells to PS-K can be predetermined based

on SOD activity in tumor tissue.

PMID: 7812358 [PubMed – indexed for MEDLINE]

PubMed

U.S. National Library of Medicine

National Institutes of Health

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Cancer, Chemotherapy, Medical Studies, PSK, Tumor

Randomized adjuvant trial to evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast cancer. 5-Year results from the Nishi-Nippon Group of the Adjuvant Chemoendocrine Therapy for Breast Cancer Organization.

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Cancer. 1992 Nov 15;70(10):2475-83.

Toi M, Hattori T, Akagi M, Inokuchi K, Orita K, Sugimachi K, Dohi K, Nomura Y, Monden Y, Hamada Y, et al.

Department of Surgery, Hiroshima University, Japan.

Abstract

BACKGROUND: A randomized adjuvant trial was conducted from October 1982 to January 1985 to evaluate the addition

of tamoxifen (TAM) to combination chemotherapy with perioperative mitomycin C (MMC) and ftorafur (FT) for patients with

estrogen receptor (ER)-positive tumors and the addition of PSK, a biologic response modifier, to MMC+FT chemotherapy

for patients with ER-negative tumors in operable Stage IIA, IIB, and IIIA cancer. The doses used were 20 mg of oral TAM

daily, 600 mg of oral FT daily, and 3 g of oral PSK daily for 2 years. Intravenous MMC (13 mg/m2) was given on the day

of operation.

METHODS: A total of 967 patients were entered and randomized by stratification based on ER status and

staging (1978 International Union Against Cancer [UICC] criteria at the time of trial execution). Of 967 patients, 914

(94.5%) were evaluable. At 5-year follow-up, significant prolonged overall survival (OS) and relapse-free survival (RFS)

times were seen with the addition of TAM in patients with ER-positive and Stage IIIA T3N0 cancer (1987 UICC-American

Joint Committee on Cancer [AJCC] criteria); however, no significant survival benefit from TAM was seen in patients with

ER-positive and Stage IIA T2N1 cancer. There was no significant difference between regimens, with or without PSK, in

patients with ER-negative disease.

RESULTS: Results of subset analyses suggested a benefit from TAM in

postmenopausal patients with ER-positive and Stage IIA T2N1 cancer and a benefit from PSK in patients with

node-negative, ER-negative, and Stage IIA T2N1 cancer.

CONCLUSIONS: The 5-year results of the current trial showed a

survival advantage by the addition of TAM to chemotherapy in patients with ER-positive and Stage IIIA T3N0 cancer.

PMID: 1423177 [PubMed – indexed for MEDLINE]

PubMed

U.S. National Library of Medicine

National Institutes of Health

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Autoimmune Disease, Breast Cancer, Cancer, Chemotherapy, Personal Testimonies

Using alternative herbal medicine instead of Chemotherapy.

Pamela Prizant says:
I had to go through chemotherapy in my early 30?s for breast cancer – if I had it to do over again I would only take the InForce and nothing else – in fact, if (God Forbid) I ever have the cancer again I will refuse taking horrible chemo and only take the InForce!! I totally believe in the InLife InForce Products and know that I am going to help people be saved from many auto-immune deficiency diseases!!

Cancer, in vitro, Medical Studies, Tumor

Anticancerous Effect of PSP Purified Products and KS-2 on Human Tumor Cell Lines in Vitro

Liang-zhong Xu, Jun Han and Gang Chen Laboratory of Pathology, Cancer Institute, Shanghai Medical University

Abstract

The anticancer effects of PSP purified products, PSP-A, PSP-B, PSP-C and crude product PSP-Cr and KS-2 were compared on four human tumor cell lines in vitro. It was found that the inhibition rate of cell proliferation of PSP-A was higher than that of PSP-Cr, PSP-B and PSP-C (P<0.05). On SPC cells, the inhibition rate of PSP-A at a dosage of 1000ug/ml was 62.7%, being the highest as compared with those on the other three cell lines.

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Cancer, Medical Studies, Prostate Cancer

Cell growth and gene modulatory activities of Yunzhi (Windsor Wunxi) from mushroom Trametes versicolor in androgen-dependent and androgen-insensitive human prostate cancer cells. TC Hsieh, JM Wu. Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA. The incidence

The incidence of prostate cancer varies greatly throughout the world; it is highest in African-Americans and lowest in the Asian populations of China, India, and Japan. Geographical differences in both prevalence of latent prostate cancer and mortality have been postulated to be influenced by diverse tumor-promoting and protective factors, both environmental and dietary. Prostate cancer is a tumor with an extremely long latency; the pattern of prostate tumorigenesis, in terms of the display and sequence of appearance of particular molecular or biochemical features, or morphological changes, characterizing different stages of the carcinogenic process, is expected to be heterogeneous. Some insights into tumor heterogeneity and progression can be obtained from studies using cell lines, particularly those derived from different anatomical sites. The present study aims to investigate whether hormone-responsive LNCaP and androgen-refractory JCA-1, PC-3, and DU-145 prostate cancer cells are responsive to Yunzhi (YZ), a proprietary dietary supplement prepared from extracts of Trametes versicolor, also known as Coriolus versicolor (a mushroom consumed by Chinese for its purported health benefits), and to elucidate its mechanism of action. Ethanolic extracts (70%) of YZ significantly reduced LNCaP cell growth, down-regulated the levels of secreted PSA, but had less effects on the expression of intracellular PSA and did not affect levels of the androgen receptor. In androgen-unresponsive prostate cancer cells, YZ had a much less pronounced suppressive effect on proliferation of PC-3 and DU-145 cells, compared to LNCaP, and was inactive against JCA-1 cells. Western blot analyses show that the expression of Rb, a key regulatory protein in G1/S transition, and PCNA, integrally involved in mammalian cell DNA replication, were significantly reduced by treatment with YZ in PC-3 and DU-145 cells, respectively. In contradiction, none of these biochemical parameters were affected in JCA-1 cells under identical treatment conditions. Further analysis shows that YZ increased the levels of signal transducer and activator family of transcription factors STAT 1 and STAT 3 in JCA-1 and not LNCaP cells. The greater sensitivity of LNCaP cells to this polysaccharopeptide raises the possibility that YZ may be considered as an adjuvant therapy in the treatment of hormone responsive prostate cancer; additionally, it may have chemopreventive potential to restrict prostate tumorigenic progression from the hormone-dependent to the hormone-refractory state.

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Cancer, Medical Studies, PSP

Coriolus versicolor polysaccharide peptide slows progression of advanced non-small cell lung cancer.

KW Tsang, CL Lam, C Yan, JC Mak, GC Ooi, JC HO, B Lam, R Man, JS Sham, WK Lam.

Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China. kwttsang@hku.hk

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths, and over 60% of patients present with advanced stages. Although polysaccharide peptides (PSP), isolated from the fungus Coriolus versicolor, have been reported to have anti-tumor effects, its clinical efficacy has not been properly evaluated. METHODS: Double-blind placebo-controlled randomized study to evaluate the effects of 28-day administration of PSP (Windsor Pharmaceutical, Hong Kong) on patients, who had completed conventional treatment for advanced NSCLC. RESULTS: Thirty-four patients, with no significant difference in their baseline demographic, clinical or tumor characteristics, or previous treatment regimes (P>0.05) were recruited into each of the PSP and control arms. After 28-day treatment, there was a significant improvement in blood leukocyte and neutrophil counts, serum IgG and IgM, and percent of body fat among the PSP, but not the control, patients (P<0.05). Although the evaluable PSP patients did not improve in NSCLC-related symptoms, there were significantly less PSP patients withdrawn due to disease progression, than their control counterparts (5.9 and 23.5%, respectively; P=0.04; OR 4.00). There was no reported adverse reaction attributable to the trial medications. CONCLUSION: PSP treatment appears to be associated with slower deterioration in patients with advanced NSCLC.

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Breast Cancer, Cancer, Chemotherapy, Medical Studies

Immunomodulatory activities of Yunzhi and Danshen in post-treatment breast cancer patients.

CK Wong, YX Bao, EL Wong, PC Leung, KP Fung, CW Lam.

Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR. China.

Breast cancer is the most common cancer among women worldwide. Discomfort and fatigue are usually arisen from anticancer therapy such as surgery, radiotherapy, chemotherapy, hormonal therapy, or combination therapy, because of the suppressed immunological functions. Yunzhi (Coriolus versicolor) can modulate various immunological functions in vitro, in vivo, and in human clinical trials. Danshen (Salvia miltiorrhiza) has been shown to benefit the circulatory system by its vasodilating and anti-dementia activity. The purpose of this clinical trial was to evaluate the immunomodulatory effects of Yunzhi-Danshen capsules in post-treatment breast cancer patients. Eighty-two patients with breast cancer were recruited to take Yunzhi [50 mg/kg body weight, 100% polysaccharopeptide (PSP)] and Danshen (20 mg/kg body weight) capsules every day for a total of 6 months. EDTA blood samples were collected every 2 months for the investigation of immunological functions. Flow cytometry was used to assess the percentages and absolute counts of human lymphocyte subsets in whole blood. Plasma level of soluble interleukin-2 receptor (sIL-2R) was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that the absolute counts of T-helper lymphocytes (CD4+), the ratio of T-helper (CD4+)/T suppressor and cytotoxic lymphocytes (CD8+), and the percentage and the absolute counts of B-lymphocytes were significantly elevated in patients with breast cancer after taking Yunzhi-Danshen capsules, while plasma slL-2R concentration was significantly decreased (all p < 0.05). Therefore, the regular oral consumption of Yunzhi-Danshen capsules could be beneficial for promoting immunological function in post-treatment of breast cancer patients.

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Cancer, Immunotherapy, in vitro, Leukemia, Medical Studies, PSP

Molecular characterization of Coriolus versicolor PSP-induced apoptosis in human promyelotic leukemic HL-60 cells using cDNA microarray.

F Zeng, CC Hon, WH Sit, KY Chow, RK Hui, IK Law, VW Ng, XT Yang, FC Leung, JM Wan.

Department of Zoology, The University of Hong Kong, Hong Kong, SAR, P.R. China.

Proteins and peptide bound polysaccharides (PSP) extracted from Basidiomycetous fungi are widely used in cancer immunotherapy and recently demonstrated to induce apoptosis in cancer cells in vitro. In order to provide the molecular pharmacological mechanisms of PSP on human cancer cells, we investigated the gene expression profiles of PSP-treated apoptotic human promyelotic leukemic HL-60 cells using ResGen 40k IMAGE printed cDNA microarray. In total 378 and 111 transcripts were identified as differentially expressed in the apoptotic cells by at least a factor of 2 or 3, respectively. Our data show that PSP-induced apoptosis in HL-60 cells might be mediated by up-regulation of early transcription factors such as AP-1, EGR1, IER2 and IER5, and down-regulation of NF-kappaB transcription pathways. Other gene expression changes, including the increase of several apoptotic or anti-proliferation genes, such as GADD45A/B and TUSC2, and the decrease of a batch of phosphatase and kinase genes, may also provide further evidences in supporting the process of PSP induced apoptosis in cancer cells. Some of the well-characterized carcinogenesis-related gene transcripts such as SAT, DCT, Melan-A, uPA and cyclin E1 were also alternated by PSP in the HL-60 cells. These transcripts can be employed as markers for quality control of PSP products on functional levels. The present study provides new insight into the molecular mechanisms involved in PSP-induced apoptosis in leukemic HL-60 cells analyzed by cDNA microarray.

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