Ganoderma lucidum (Reishi mushroom) for cancer treatment

Each year, the number of patients diagnosed with cancer has been rising. It is the world’s second leading cause of death and a significant public health issue. Cancer patients are treated with a variety of treatments, including chemotherapy, surgery, hormone therapy, medications, and so on. Chemotherapy and radiation are two common cancer treatments in conventional medicine. These two regimens are associated with a number of side effects, including, gastrointestinal pain, weariness, and even cardiac, pulmonary, and neurological damage. These adverse effects have had an impact on patients and have reduced their quality of life. As a result, various oncology studies have been started during the last few decades in effort to develop an alternative cancer drug. Ganoderma lucidum (G. lucidum) is one such compound that has received a lot of attention in traditional Chinese medicine. [1]

Ganoderma is a major source of natural fungal medicines with numerous pharmacological activity. It is regarded as “the king of herbs”. It is widely used in China, Korea, the United States, Japan, and other nations. [2] It has been used for many years to treat cancer disorders. It has three main features i.e. it does not produce side effects, does not only act on particular organs, and supports the normal function of organs. It contains the major active constituent’s polysaccharides and triterpenoids and have carcinostatic effects on a variety of cancer cell lines, including those from the prostate, pancreatic, breast, lung, skin, colon, and liver. They have an effect on several phases of cancer development. [3-4]

Components of G. lucidum and their function

• Triterpenes induce apoptosis in cancer cell lines through mitochondria-dependent pathways.[4]
• Polysaccharides have the ability to boost the immune system of the host. by promoting the formation of macrophages, NK cells, and T lymphocytes; limiting tumor-derived angiogenesis; and inhibiting the release of angiogenic factors such as VEGF and TGF- β1. [4]
• Triterpenoids derived from lucidum, such as ganoderic acids T-Z, inhibited cytotoxic activity on hepatoma cells. [5]
• The amino-polysaccharide fraction of lucidum inhibited reactive oxygen species, which have been linked to cancer pathogenesis. [6]
• Polysaccharides inhibit the movement of the cancer cells i.e. metastasis. [4]

 Studies of G. lucidum against cancer treatment

Human studies

• Patients who received G. lucidum extract as part of their anticancer treatment plan were 1.27 times more prone to respond to chemotherapy or radiotherapy than those who did not. G. lucidum could enhance host immune processes by significantly increasing the percentages of CD3, CD4, and CD8 lymphocytes. Patients in the G. lucidum group had a better quality of life after therapy than those in the control group. [1]
• Treatment of prostate cancer patients with Ganoderma-containing PC-SPES resulted in a substantial decline in prostate-specific antigen levels. [7]
• A 6-month therapy with lucidum boosted mitogen-induced lymphoproliferative responses in immune compromised children with malignancies. [8]
• lucidum spore powder improved cancer-related fatigue and quality of life in 48 breast cancer patients on endocrine therapy, with no notable side effects. [9]
• Five patients with gynecological cancer demonstrated disease stability after consuming Ganoderma in the form of fruit body and spores. [10] When the mushroom combined with regular chemotherapy, it provided some benefit. [11]
• lucidum improved immune responses in 134 patients with advanced-stage cancer by increasing the number of CD3+ cells. [12]
• 68 lung cancer patients whose immunological markers, such as total T cells, NK cells, and the CD4/CD8 ratio, were considerably improved in the lucidum-treated group. [13]

Animal studies

• In mice, oral mycelial extract supplementation dramatically reduced lung adenoma formation. Oral administration of triterpenoid fractions for 18 days inhibited Martigel-induced angiogenesis, significantly reducing tumor mass and the number of tumor cell colonies that had spread to the liver in female C57BL/6J strain mice with intrasplenic insertion of Lewis lung cancer cells. [14]
• A β-(1→3) glucan from crude lucidum inhibited tumor growth by 90%. [15]
• lucidum dry powder formulation inhibited tumor growth and increased life duration in both allogeneic sarcoma-180-bearing ddY mice and synergenic MM-46 mammary tumor-bearing C3H/He mice. [16]
• luciduminhibits the tumor growth and invasion in PC-3-implanted mice. [17]
• Polysaccharide fraction from the fruit body inhibits the development of transplanted sarcoma 180 tumor cells in mice. [18]
• lucidumwas found to prolong the life span of tumor-transplanted mice by inhibiting metastasis to the lung. [19]
• The triterpenoid of G lucidum suppressed primary solid-tumor growth in the spleen, liver metastasis, and secondary metastatic tumor growth in the liver, which were originally induced by the intrasplenic implantation of the LLC in mice. [20]

Refrences

[1]. Jin X, Ruiz Beguerie J, Sze DM, Chan GC. Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev. 2016 Apr 5;4(4):CD007731. doi: 10.1002/14651858.CD007731.pub3. PMID: 27045603; PMCID: PMC6353236.

[2] Kim SS, Kim YS.Korean Mushrooms. Seoul: Yupoong; 1990:298-299.

[3]Suprasert, P., Apichartpiyakul, C., Sakonwasun, C., Nitisuwanraksa, P., Phuackchantuck, R., 2015. A randomized double blinded study of Ganoderma Lucidum (Lingzhi) in salvage setting of recurrent gynecologic cancer. Int. J. Cancer Clin. Res. 2.

[4] Kao, C.H., Bishop, K.S., Xu, Y., Han, D.Y., Murray, P.M., Marlow, G.J., Ferguson, L.R., 2016. Identification of potential anticancer activities of novel Ganoderma lucidum extracts using gene expression and pathway network analysis. Genomics Insights 9 pp.GEI-S32477.

[5] Lin, C.N., Tome, W.P., Won, S.J., 1991. Novel cytotoxic principles of Formosan Ganoderma lucidum. J. Nat. Prod. 54 (4), 998–1002.

[6] Pincemail JJ. Free radicals and antioxidants in human diseases. In: Favier AE, Cadet J, Kalyanaraman B, Fontecave M, Pierre JL, eds. Analysis of Free Radicals in Biological Systems. Berlin, Germany: Birkhauser Verlag; 1995:83-98.

[7] Gao Y, Zhou S. Cancer prevention and treatment by Ganoderma, a mushroom with medicinal properties. Food Rev Int. 2009;19:275–325.

[8] Shing, M. K., Leung, T. F., Chu, Y. L., Li, C. Y., Chik, K. W., Leung, P. C., et al. (2008). Randomized, double-blind and placebo-controlled study of the immunomodulatory effects of Lingzhi in children with cancers. J. Clin. Oncol. 26(15 Suppl.), 14021–14021. doi: 10.1200/jco.2008.26.15_suppl.14021.

[9] Zhao, H., Zhang, Q., Zhao, L., Huang, X., Wang, J., and Kang, X. (2012). Spore powder of Ganoderma lucidum improves cancer-related fatigue in breast cancer patients undergoing endocrine therapy: a pilot clinical trial. Evid. Based Complement. Altern. Med. 2012:809614. doi: 10.1155/2012/809614.

[10] Suprasert, P., Apichartpiyakul, C., Sakonwasun, C., Nitisuwanraksa, P., and Phuackchantuck, R. (2014). Clinical characteristics of gynecologic cancer patients who respond to salvage treatment with Lingzhi. Asian Pac. J. Cancer Prev. 15, 4193–4196. doi: 10.7314/APJCP.2014.15.10.4193.

[11] Chen, Q. M., and Alpert, J. S. (2016). Nutraceuticals: evidence of benefit in clinical practice? Am. J. Med. 129, 897–898. doi: 10.1016/j.amjmed.2016.03.036.

[12] Gao, Y., Zhou, S., Jiang, W., Huang, M., and Dai, X. (2003). Effects of ganopoly (a Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients. Immunol. Invest. 32, 201–215. doi: 10.1081/IMM-120022979.

[13] Gao Y. H, Sai X. H, Chen G. L, Ye J. X, Zhou S. F. A randomized, placebo-controlled, multi-center study of Ganoderma lucidum (W. Curt.: Fr.) Lloyd (Aphyllophoromycetideae) polysaccharides (Ganopoly) in patients with advanced lung cancer. Int J Med Mushrooms. 2003;5:368–81.

[14] Kimura Y, Taniguchi M, Baba K. Antitumor and antimetastatic effects on liver of triterpenoid fractions of Ganoderma lucidum: Mechanism of action and isolation of an active substance. Anticancer Res. 2002;22:3309–18.

[15]Ohno N, Miura N. N, Sugawara N, Tokunaka K, Kirigaya N, Yadomae T. Immunomodulation by hot water and ethanol extracts of Ganoderma lucidum. Pharm Pharmacol Lett. 1998;4:174–7.

[16] Nonaka Y, Shibata H, Nakai M, editors. et al. Anti-tumor activities of the antlered form of Ganoderma lucidum in allogeneic and syngeneic tumor-bearing mice. Biosci Biotechnol Biochem. 2006;70:2028–34.

[17] Evans S, Dizeyi N, Abrahamsson P. A, Persson J. The effect of novel botanical agent TBS-101 on invasive prostate cancer in animal models. Anticancer Res. 2009;29:3917–24.

[18] Miyazaki T, Nishijima M. Studies on fungal polysaccharides. XXVII. Structural examination of a water-soluble, antitumor polysaccharide of Ganoderma lucidum. Chem Pharm Bull. 1981;29:3611–16.

[19] Lee S. S, Wei Y. H, Chen C. F, Wang S. Y, Chen K. Y. Antitumor effects of Ganoderma lucidum. J Chin Med. 1995;6:1–12.

[20] Kimura Y, Taniguchi M, Baba K. Antitumor and antimetastic effects on liver triterpenoid fractions of Ganoderma lucidum: mechanism of action and isolation of an active substance. Anticancer Res. 2002;22(6A):3309-3318.