Premier on medicinal fungus as effective adjuvant & complementary agents for cancer therapy
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This document discusses cancer, its characteristics, current cancer treatment approaches, and the potential for using medicinal mushrooms and their compounds as complementary and adjuvant cancer therapies. It provides information on several medicinal mushrooms - Coriolus versicolor, Phellinus linteus, Antrodia camphorata, and their extracted compounds. Studies show combinations of chemotherapy and these mushrooms/compounds can be more effective than chemotherapy alone in treating cancers like lung cancer and liver cancer. The compound Antroquinonol isolated from A. camphorata has been shown to inhibit the growth of various cancer cell types and has a high safety profile.
Premier on medicinal fungus as effective adjuvant & complementary agents for cancer therapy
- 1. Mr. LEE Chee Cheow (M.Sc.) Chief Scientific Officer, International Advanced Bio-Pharmaceutical Industries Pte Ltd. Promoting the Nutriceutical Science of Preventive Self-care Effective Adjuvant & Complementary Agents for Cancer Therapy Medicinal Fungus
- 2. Cancer Etiolopathology Characteristics of Cancer Cells The problem: Cancer cells divide rapidly (cell cycle is accelerated) They are “immortal” Cell-cell communication is altered Uncontrolled proliferation Invasiveness Ability to metastasise Current major approaches to Therapy of cancers Six Established Rx Modalities: 1. Surgery 2. Radiotherapy 3. Chemotherapy 4. Endocrine therapy 5. Immunotherapy 6. Targeted therapy
- 3. Current Cancer Treatment • Rarely is a single agent effective • Rather, multiple agents and treatment modalities are used
- 4. SYNERGY (Chemo + TCM) Cancer Treatment is more effective than Chemo or TCM alone Study Centers Treatment Group Patient size Median Survival Time (months) Lin xx (8 hospitals) Synergy Chemo TCM 199 215 173 12.03 8.46 10.92 Chou xx (6 hospitals) Synergy Chemo TCM 103 92 99 11.8 7.9 9.7 Liu & Fan (10 Hospitals) Synergy Chemo TCM 137 146 74 19.4 14.53 14.02 Results of multi-center, randomized, parallel, controlled, prospective study methods to evaluate the effectiveness and safeness of using Synergy Medicine treatment in advanced NSCLC patients. Extract from clinical presentation at SGH on “Demonstration of Synergy Medicine treatment research in advanced non-small cell lung cancer” by Prof. Liu Jia Xiang & Prof. Fan Zhong Ze , Shanghai University of TCM.
- 5. Chemotherapy drugs • They are Anti- proliferative – i.e. they damage DNA and so initiate apoptosis (programmed cell dead). • They also affect rapidly dividing normal cells – e.g. bone marrow, hair follicles, sperm forming cells. TISSUE TYPE UNDESIRED EFFECTS Bone marrow Low white blood cell > infection risk Immunosuppression Low red blood cell > Anemia GI tract Oral or intestinal ulceration; Diarrhea Hair follicles Alopecia (Hair loss) Gonads Menstrual irregularities, including premature menarche; impaired spermatogenesis Wounds Impaired healing Fetus Teratogenesis (especially during first trimester) Adverse Drug Reactions (side effects) of Anti-neoplastic (Chemo) Drugs
- 6. Adjuvant & Complementary Cancer Treatments Goals: Helps potentiate the efficacies of existing anti-cancer chemotherapeutical drugs. Helps eradicate microscopic cancer after surgery Helps alleviate symptoms and prevents the decline in immunity Avoidance of life-threatening toxicity Increased survival and improved quality of life
- 7. Medicinal mushrooms Many Pharmaceuticals are derived from the Fungus Kingdom: • Penicillin (antibiotic) • Ciclosporin (immunosuppressant) • Griseofulvin (antifungal) • Statins (cholesterol lowering) • Mushrooms are prebiotic • They have immune system enhancement properties • They are anti tumour agents
- 8. Mushrooms (Fungus): source of potent natural based Chemopreventive Agents
- 9. Anti cancer compound isolated from mushrooms Compound From Fungus Antroquinonol Antrodia camphorata Cordycepin Cordyceps (Cordyceps militaris) Ganoderic acid Reishi (Ganoderma lucidum) Grifolin Albatrellus confluens Hispolon Phellinus linteus Illudin-S Omphalotus illudens Lentinan Shiitake (Lentinula edodes) Psilocybin Psilocybin mushrooms
- 10. Polysaccharide of Coriolus versicolor (Turkey Tail) Pharmacology: • Anticarcinogen • Antiproliferative • Immunological regulator A mushroom used in traditional Asian herbal remedies. GEN PHARMAC 30;1:1--4, 1998. © 1998 Elsevier Science Inc. Polysaccharide peptide (PSP): • isolated 1983 in China. • PSP is currently research in many countries for use as an anti-tumor drug.* • PSP immunologic activity is hypothesized to be the main underlying mechanism responsible for its antitumor effects as well as its impact on survival rates. * Phase 1 Clinical Trial of Trametes versicolor in Women with Breast Cancer; International Scholarly Research Network, ISRN Oncology Volume 2012, Article ID 251632 Polysaccharide K (PSK): • In 1980s, Japanese government approved the use of PSK for treating several types of cancer. • PSK is a best-selling anti-cancer drug in Japan, where it is currently used as a cancer treatment along with surgery, chemotherapy, and radiation therapy. Two substances extracted from the mushroom:
- 11. Polysaccharide-peptide (PSP) of Coriolus versicolor Pharmacological Actions： control the growth of tumour cells • lung cancer • stomach cancer • lymphoma • leukemia • sarcoma-180 Clinical applications: • Adjuvant to chemo & radiation therapy • Significantly improved immunity of immune suppressed patients during treatment, reduce toxicity caused by chemotherapy. • Relieve symptoms of: fatigue, nausea, vomiting, dry mouth, anxiety, cold sweating. • Improve appetite, relieve pain, improve sleep quality, improve overall quality of life of patients during treatment. • PSP activates monocytes in resting human peripheral blood mononuclear cells: Immunomodulatory implications for cancer treatment; Food Chemistry, Volume 138, Issue 4, 15 June 2013, Pages 2201-2209 • A review of research on the protein-bound polysaccharide (polysaccharopeptide, PSP) from the mushroom Coriolus versicolor Review Article; General Pharmacology: The Vascular System, Volume 30, Issue 1, January 1998, Pages 1-4
- 12. Phellinus linteus • Medicinal mushroom Phellinus linteus (Berk. et Curt.) has been used in traditional oriental medicine in Japan, China & Korea. • Study in Japan demonstrated that PL has strongest anti tumor effects compared to other mushrooms. Anti tumor Biological activities • ANGIOGENESIS • APOPTOSIS • CHEMOPREVENTION • Anti INVASIVE • Anti PROLIFERATION Other pharmacological effects: • immunomodulatory • anti-inflammatory • anti-allergic • anti-oxidant Anticancer Effect of Phellinus linteus ; Potential Clinical Application in Treating Pancreatic Ductal Adenocarcinoma; Kang et al., J Carcinogene Mutagene 2013, S9
- 13. Phellinus linteus Medicinal mushroom Phellinus linteus as an alternative cancer therapy (Review); Experimental and therapeutic medicine 1: 407-411, 2010
- 14. Antrodia Camphorata: A Rare Fungus World’s most valuable medicinal fungus compared: Bio-Active Ingredients Ganoderma Lucidium Antrodia Camphorata Bio Active Triterpenes 20-50 types >200 types Triterpenes concentration 1 – 3 % 10-45 % AC is highly priced for its effectiveness in treating the following ailments over centuries in Taiwan: • Anti-cancer • Improve liver functions • Anti Fatigue • Anti-inflammation • Anti-hepatitis infection • Improve immunity • Anti-allergenic
- 15. Product Information : IMMUNO CPX: A cancer therapeutic formulation developed by 2 Taiwan medical University in collaboration with Japan genetic research institute, base on immunotherapy approach. Indication: • Used as a immunotherapy adjuvant to cancer treatment along with surgery, chemotherapy and radiation therapy. • Helps to potentiate the efficacies of existing anti-cancer chemotherapeutical drugs. • Helps alleviate symptoms and prevents the decline in immunity. INGREDIENT: • Antrodia camphorata mycelium • Phellinus linteus mycelium • Coriolus versicolor polysaccharide • Extractum curcumae longae Immunotherapy: A New Anticancer Approach Also called biological therapy, immunotherapy aims to boost a person's immune system to fight disease. Clinical application:
- 16. KEY FEATURES: High Safety No Resistant for Liver Cancer and others cancer therapies from non-option patient experience • USFDA Patent 7342137 Mar.11,2008 • USFDA Patent 7385088 Jun.10,2008 • USFDA Patent 7411003 Aug.12,2008 • USFDA Patent 7456225 Nov.25,2008 • USFDA Patent 7501454 Mar.10,2009 • USFDA Patent 7468392 Dec.23.2008 Antroquinonol® High safety High performance Anti cancer compound Based on Human Cancer Cell, Antroquinonol® can Assist the Treatment of Multiple Therapies in Solid Tumor. New Anti Cancer Compound Isolated from Antrodia Camphorata OH O O O 1 2 3 4 5 6 22 7 8 9 21 10 11 12 13 20 14 15 16 17 18 19 23 24 Safety: Orally active with high safety profile: 1. MTD in Rat : >100 mg/kg/day; 2. No System toxicity in Rat & Dog: 100 mg/kg/day 3. LD50>1,000mg/kg/day in Dogs 4. NOEL (No Observed Effect Level) Teratology : >80 mg/kg 5. NOAEL (No Observed Adverse Effect Level) in Rat & Dog = 30 mg/kg/day
- 17. Wide spectrum anti solid tumor effects BROAD SPECTRUM ANTI CANCER PROPERTIES: Antroquinonol inhibited the growth of various types of cancer cells in culture
- 18. NS398 (COX-2 inhibitor) AC (110mg/kg) AC (55mg/kg) Control Source: Antrodia camphorata inhibits proliferation of human breast cancer cells in vitro and in vivo. Food and Chemical Toxicology 46 (2008) 2680–2688 Effective In vivo inhibition of MDA- MB-231 Breast cancer tumor Comparison against COX-2 inhibitor Anti Breast Cancer Properties
- 19. Antroquinonol inhibits NSCLC proliferation by altering PI3K/mTOR proteins and miRNA expression profiles; Mutation Research 707 (2011) 42–52 Lung Cancer cells: Anti proliferative effect
- 20. Liver Cancer cells: Anti proliferative effect Antroquinonol displays anticancer potential against human hepatocellular carcinoma cells: A crucial role of AMPK and mTOR pathways; Biochem Pharmacol. 2010 Jan 15;79(2):162-71. PMID:19723512
- 21. Source: The Augmented Anti-Tumor Effects of Antrodia camphorata Co-Fermented with Chinese Medicinal Herb in Human Hepatoma Cells; The American Journal of Chinese Medicine, Vol. 37, No. 4, 771–783; Adjuvant with cisplatin & paclitaxel 26 Anti Liver Cancer Properties HepG2 Liver Cancer cells
- 22. Source: The adjuvant effects of Antrodia Camphorata extracts combined with anti-tumor agents on multidrug resistant human hepatoma cells. Journal of Ethnopharmacology 118 (2008) 387–395 Anti Liver Cancer Properties Adjuvant with Chemotherapy Multidrug resistant (A)C3A & (B)PLC/PRF/5 hepatoma cells
- 23. • Under go targeted chemo therapy • Nesavar (Sorafenib) 30 days Clinical Case Report Patient (Diabetic with Kidney Dialysis): • Suffered from primary Liver cancer. • 4 months after Liver resection, • Diagnose with late stage metastatic Lung cancer. Diagnose with late stage metastatic Lung cancer. CT scan show continue presence of Tumor • Change chemo regime • Take Antroquinonol 400mg / day x 24 days CT scan show complete absence of Tumors
- 24. Antroquinonol® isolated from AC Functions of Antroquinonol in adjuvant and combination chemotherapy: • Increased cancer cell kill : • Administration of drugs with different mechanisms of action. • Suppression of drug resistance • Helps reduced injury to normal cells : • It provide Hepatoprotection against drug toxic side effects • Support Immunity against infections Clinical application: Antroquinonol is currently use as adjuvant/combination agent to existing chemotherapy or as primary agent for non options cancer patients. December 2013: Antroquinonol is approved by US FDA enter into phase 2 clinical trial (NCT01134016)
- 25. Common Symptoms of Cancer Palliative Care Outpatients • Pain 82% • Easy fatigue 67% • Weakness 64% • Anorexia 64% • Weight loss 60% • Lack of energy 59% • Dry mouth 55% • Constipation 51% • Dyspnea 51% • Easy satiety 50% • Sleep problems 47% • Depression 40% Adapted from Donnelly et al.
- 26. Cancer Type Range Early disease 48% (38%-100%) Advanced disease 74% (53%-100%) Pancreas 72%-85% Esophagus 71%-77% Head & neck 67%-91% Genitourinary 58%-90% Prostate 56%-94% Breast 40%-89% Prevalence of Cancer Pain Cancer Pain: Assessment and Management. 2003:38-50:
- 27. Common Cancer Pain by Pathophysiology • Bone metastases • Skin lesions • Malignant bowel obstruction • Chemotherapy-induced peripheral neuropathy Causes of Cancer Pain (Etiology) Prevalence Due to cancer 85%-93% Due to diagnosis & treatment 17%-21% Unrelated to diagnosis & treatment 2%-9% Pain;1995:63;65-76 Pain;1999:82:263-274 Causes of Cancer Pain
- 28. Isolated from Antrodia Camphorata
- 29. Isolated from Antrodia Camphorata
- 30. Effective chemopreventive agents: Multi-pronged anti cancer approach Wide spectrum cancer (type) targets Cancer Chemoprevention Anti-cancer Anti cell promotion Anti cell proliferation Activate cell death Anti-toxin Detoxification, strengthen liver functions Anti-infection Strengthen immune systems Anti-oxidation Major categories of chemopreventive agents
- 31. Treatment stages Pre-Cancer therapy During Chemotherapy Post Chemotherapy Application Mode: Neo-Adjuvant / Complimentary Adjuvant Preventive Therapeutic Actions: Anti oxidation Anti infection Anti inflammation Hepatoprotection Immune modulation Tumor regression Chemoprevention Immune modulation Anti oxidation AC in Cancer Applications Summary Anti Initiation Anti oxidation Anti inflammation Anti Promotion • Growth inhibition Anti Progression • Induce apoptosis AC simultaneously attack the various stages of cancer formation Antrodia Camphorata Powerful Natural Chemopreventive Compound
- 32. Centre for Adjuvant & Complementary Medicine Company focus on offering Breakthrough Bio-Medical Product Solutions in major areas of Aging Health Concerns that helps in the Prevention of Chronic Illnesses of Modern Society, Extending and Enhancing the Quality of Life. Company sub specialized in providing Pharmacological Therapy product solutions for: Chronic disease management Critical illness recovery Complimentary chemotherapy High risk chemoprevention INTERNATIONAL ADVANCED BIO-PHARMACEUTICAL INDUSTRIES PTE LTD 8 Boon Lay Way, #08-03 TradeHub 21, Singapore 609964 Tel: +65-68738693 Fax: +65-68738694 URL: www.iabpi.com 李咨潮 硕士 Mr LEE Chee Cheow (M.Sc. TCM Dip.) 科学主任 首席咨询顾问 Chief Scientific Officer Principal Consultant, IABPI Author: Chief Scientist, CAM Pharmacologist & Nutriceutical Consultant Areas of research interest includes: Naturopathic & Integrated Medicine Chemopreventive Therapy Transdermal Drug Delivery system.