MUSHROOMS AND CANCER

(from Medicinal Mushrooms – A Clinical Guide)

Cancer has traditionally been one of the main conditions for which mushrooms have been used and in the Far East several mushroom extracts are licensed as adjuvant nutrition for cancer therapy, including:

• PSK and PSP - Proteoglycan extracts from Trametes versicolor mycelium
• Lentinan - Polysaccharide extract from Lentinus edodes fruit body
• Schizophyllan - Polysaccharide extract from Schizophyllan commune culture broth

These extracts have impressive risk/benefit profiles with large scale clinical trials demonstrating extended survival times in a range of cancers and a complete absence of serious side effects¹.

Medicinal mushrooms' broad range of immunological effects make them ideally suited for support in cases of cancer, with the ability to:

• Facilitate a more effective immune response to the cancer
• Increase tumor cell apoptosis and inhibit tumor growth and metastasis
• Increase the efficacy and reduce the side effects of conventional treatment

Can Medicinal Mushrooms be used with Chemotherapy?

Mushroom extracts, such as PSK and PSP, are routinely prescribed alongside many different chemotherapeutic agents, including cyclophosphamide, Mitomycin C and 5-Fluorouracil, reducing the side effects of chemotherapy, including nausea, hair loss and lowered immune status, as well improving appetite, general condition and haematopoietic parameters ^2-10.

Many other mushroom extracts have shown synergistic activity with chemotherapeutic drugs including:

• Lentinan extends survival in inoperable or recurrent gastric cancer in conjunction the tegafur with a 50% survival time of 173 days compared to 92 days with tegafur alone¹¹. Lentinan has also been shown to inhibit Th2 activity and increase Cytotoxic T-cell activity in the spleen when administered to gastric cancer patients undergoing chemotherapy.
• Armillaria mellea polysaccharide protected mice bone marrow cells from damage by cyclophosphamide¹².
• Hericium erinaceus enhances doxorubicin-induced apoptosis in liver cancer cells¹³.
• Ganoderma lucidum triterpenes enhance doxorubicin-induced apoptosis in HeLa (cervical cancer) cells and prevent cisplatin-induced nephrotoxicity ^14,15.
• Maitake polysaccharide fractions potentiate the action of carmustine and increase efficacy when given in combination with chemotherapy across a range of cancers, as well as reducing cisplatin-induced nephrotoxicity¹⁶.
• A hot-water extract of Cordyceps sinensis significantly enhanced recovery from taxol-induced leukopenia in mice¹⁷.
• Polysaccharide extract from S. commune enhanced recovery of cellular immunity after chemotherapy ^18,19.

It appears likely that, as well as supporting the immune system and ameliorating the immune suppression induced by many chemotherapy drugs, mushroom polysaccharide extracts may also contribute to the efficacy of the drugs themselves through enhanced production of reactive oxygen species (ROS). Liu et al reported an increase in ROS and reactive nitrogen intermediates in peritoneal macrophages in mice given PSP²⁰. Grifron-D, a polysaccharide from Grifola frondosa, has also been shown to have a direct cytotoxic effect on cancer cells through oxidative membrane damage leading to apoptosis²¹.

Although mushrooms also show anti-oxidant activity, this is strongly correlated with pro-oxidant activity, as well as with their respective polysaccharide and polyphenol content, indicating that possible excess cell defense−related intracellular ROS generated by mushroom extracts may be downregulated by the antioxidant components present in the same extracts²².

CLINICAL NOTE
Medicinal mushrooms may also offer some protection against venous thromboembolism (VTE), which some chemotherapy drugs are known to increase the risk of (the annual incidence of VTE in patients receiving chemotherapy is estimated at 11% and this can climb to 20% or higher depending on the type of drug(s) being administered)²³. Elderly patients are especially at risk and mushrooms with anti-coagulant properties (such as G. lucidum and Tremella fuciformis) can be useful in such cases.

Caution - Because of medicinal mushrooms' ability to support immune function in patients receiving chemotherapy, they are contraindicated with immunosuppressive chemotherapy for autoimmune conditions.


Can Medicinal Mushrooms be used with Radiotherapy?

As with chemotherapy, evidence for synergistic benefit between medicinal mushrooms and radiotherapy is widespread, including:

• Tremella fuciformis polysaccharide extract markedly improved the recovery rate of hemopoiesis in irradiated mice, with increased nucleated cells in the bone-marrow and endogenous colonies in the spleen, without apparent effect on cell radio-sensitivity. In a trial with 136 patients undergoing radiotherapy, oral consumption of T. fuciformis polysaccharide extract (3g/day) resulted in a 13.2% reduction in WBC compared to a 35.2% reduction in the control group ^24,25. Other experiments on dogs and monkeys confirm the benefits of T. fuciformis polysaccharides in protecting against the effects of Cobalt-60 radiation²⁶.
• PSP in combination with radiotherapy significantly increased the percentage of apoptotic cells at 24hr compared to radiation alone and reduced radiotherapy induced reduction in white blood cell count²⁷.
• Trametes versicolor biomass (6g/day) prevented decreases in red and white blood cells in lung cancer patients undergoing radiotherapy²⁸.
• Hot water extract from Cordyceps sinensis protected mice from radiation-induced bone marrow and intestinal damage²⁹.

Can Medicinal Mushrooms be used with Surgery?

Mushroom extracts such as PSK and Lentinan are routinely used alongside surgical excision of tumours with no contraindication. In addition, two double-blind placebo-controlled studies at Harvard Medical School showed beta-glucan (2g/day) to be effective at protecting patients from infection after undergoing major surgery, indicating their role in enhancing host immunity ^1,2.

CLINICAL NOTE
Mushrooms with anti-coagulant properties are best avoided immediately before surgery. The main mushrooms in this category are Antrodia camphorata, Auricularia auricula, Ganoderma lucidum and Tremella fuciformis.

1. The use of mushroom glucans and proteoglycans in cancer treatment. Kidd P.M. Altern Med Rev. 2000;5(1):4-27.
2. Advances in immunomodulating studies of PSP. Li K.Y. Hong Kong Assoc. for Health Care Ltd. 1999;Advanced Research in PSP:39-46.
3. A new biological response modifier - PSP. Yang Q.Y, Yi J.H, Li X.Y. 1993;PSP International Symposium:56-72
4. Polysaccharide peptide (PSP) restores immunosuppression induced by cyclophosphamide in rats. Qian Z.M, Xu M.F, Tang P.L. Am J Chin Med. 1997;25(1):27-35.
5. Tsukagoshi S.Y, Hashimoto G, Fujii H, Kobayashi K, Nomoto, Orita K. Krestin (PSK). Cancer Treatment Review. 1984;11:131-155.
6. Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT) on human leukemia HL-60 cells. Wan J.M, Sit WH, Yang X, Jiang P, Wong L.L. Chin Med. 2010;5:16.
7. Polysaccharopeptide enhances the anticancer activity of doxorubicin and etoposide on human breast cancer cells ZR-75-30. Wan J.M, Sit W.H, Louie J.C. Int J Oncol. 2008;32(3):689-99
8. Enhancement of anti-cancer activity of cisdiaminedichloroplatinum by the protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) in vitro. Kobayashi Y, Kariya K, Saigenji K, Nakamura K. Cancer Biother. 1994;9(4):351-8.
9. Antitumor effect of PSK and its combined effect with CDDP on ovarian serous adenocarcinoma-bearing nude mice. Ishii K, Kita T, Hirata J, Tode T, Kikuchi Y, Nagata I.
Nippon Sanka Fujinka Gakkai Zasshi. 1993;45(4):333-9.
10. Effects of PSK on interleukin-2 production by peripheral lymphocytes of patients with advanced ovarian carcinoma during chemotherapy. Kikuchi Y, Kizawa I, Oomori K, Iwano I, Kita T, Kato K. Jpn J Cancer Res. 1988;79(1):125-30.
11. End-point result of a randomised controlled study on the treatment of gastrointestinal cancer with a combination of Lentinan and chemotherapeutic agents. Taguchi T, Furue H et.al. Excerpta Medica. 1985:151-165
12. Protective effect of Armillaria mellea polysaccharide on mice bone marrow cell damage caused by cyclophosphamide. Li Y.P, Wu K.F, Liu Y. Zhongguo Zhong Yao Za Zhi. 2005;30(4):283-6.
13. Hericium erinaceus enhances doxorubicin-induced apoptosis in human hepatocellular carcinoma cells. Lee J.S, Hong E.K. Cancer Lett. 2010 May.
14. Interaction of Ganoderma triterpenes with doxorubicin and proteomic characterization of the possible molecular targets of Ganoderma triterpenes. Yue Q.X, Xie F.B, Guan S.H, Ma C, Yang M, Jiang B.H, Liu X, Guo D.A. Cancer Sci. 2008;99(7):1461-70.
15. Prevention of cisplatin induced nephrotoxicity by terpenes isolated from Ganoderma lucidum occurring in southern parts of India. Pillai TG, John M, Sara Thomas G. Exp Toxicol Pathol. 2009 Dec.
16. Maitake beta-glucan enhances therapeutic effect and reduces myelosupression and nephrotoxicity of cisplatin in mice. Masuda Y, Inoue M, Miyata A, Mizuno S, Nanba H. Int Immunopharmacol. 2009;9(5):620-6.
17. Cordyceps sinensis health supplement enhances recovery from taxol-induced leukopenia. Liu W.C, Chuang W.L, Tsai M.L, Hong J.H, McBride W.H, Chiang C.S. Exp Biol Med (Maywood). 2008;233(4):447-55.
18. Clinical evaluation of sizofran as assistant immunotherapy in treatment of head and neck cancer. Kimura Y et al. Acta Otolarynzology. 1994;511:192-195
19. Activated (HLA-DR+) T-lymphocyte subset in cervical carcinoma and effects of radiotherapy and immunotherapy with sizofiran on cell-mediated immunity and survival. Miyazaki K et al. Gynaecology and Oncology. 1995;56:412-420
20. Activation of peritoneal macrophages by polysaccharopeptide from the mushroom, Coriolus versicolor. Liu W.K, Ng T.B, Sze S.F, Tsui K.W. Immunopharmacology. 1993;26(2):139-46.
21. Induction of apoptosis in human prostatic cancer cells with beta-glucan (Maitake mushroom polysaccharide). Fullerton S.A, Samadi A.A, Tortorelis D.G, Choudhury M.S, Mallouh C, Tazaki H, Konno S. Mol Urol. 2000;4(1):7-13.
22. Pro- and antioxidative properties of medicinal mushroom extracts. Wei S, Griensven LJLD. Int J Med Mushr. 2008;10(4):30
23. Chemotherapy-induced thrombosis. Haddad T.C, Greeno E.W. Thromb Res. 2006;118(5):555-68.
24. The effect of Tremella polysaccharides on leukopoenia following radiotherapy. Dai H. Chinese Pharmaceutical Journal 2006;41(13)p:1033-4
25. Radioprotective mechanism of preparation extracted from TFB . Effects on hemopoietic system in mice Xu C.X, Li Z.W, Yang F.T, Niu H.S, Liu S.H and Lu R.S Acta Academiae Medicinae Sinicae. 1984-05
26. Effect of Tremella fuciformis Berk on acute radiation sickness in dogs. Zhao T.F, Xu C.X, Li Z.W, Xie F, Zhao Y.T, Wang S.Q, Luo C.H and Lu R.S, Ni G.L , Ku Z.Q, Ni Y.F, Qian Q, Chen X.Q. Acta Academiae Medicinae Sinicae. 1982-01
27. The ameliorative effect of PSP on the toxic and side effect reactions of chemo- and radiotherapy of cancers. Advanced research in PSP. Sun Z et al. Hong Kong Association for Health Care Ltd. 1999:304-307
28. The use of Coriolus-MRL supplementation in lung cancer patients undergoing radiotherapy. Catita J. Mycology News. 2000;1(4):3-4

29. Protection against radiation-induced bone marrow and intestinal injuries by Cordyceps sinensis, a Chinese herbal medicine. Liu W.C, Wang S.C, Tsai M.L, Chen M.C, Wang Y.C, Hong J.H, McBride W.H, Chiang C.S. Radiat Res. 2006;166(6):900-7
30. A phase II multicenter, double-blind, randomized, placebo-controlled study of three dosages of an immunomodulator (PGG-glucan) in high-risk surgical patients. Babineau T.J, Hackford A, Kenler A, Bistrian B, Forse R.A, Fairchild P.G, Heard S, Keroack M, Caushaj P, Benotti P. Arch Surg. 1994;129(11):1204-10.
31. Effect of PGG-glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations. Betafectin Gastrointestinal Study Group. Dellinger E.P, Babineau T.J, Bleicher P, Kaiser A.B, Seibert G.B, Postier R.G, Vogel S.B, Norman J, Kaufman D, Galandiuk S, Condon R.E. Arch Surg. 1999;134(9):977-83.