Ganoderma: A Cancer Immunotherapy Review

Abstract

Ganoderma is a significant source of natural fungal medicines and has been used for the treatment of various diseases for many years. However, the use of Ganoderma in cancer immunotherapy is poorly elucidated. In this study, we have analyzed 2,398 English-language papers and 6,968 Chinese-language papers published between 1987 and 2017 by using bibliometrics. A steady growth in the number of publications was observed before 2004, followed by an exponential increase between 2004 and 2017. The most common category for publications about Ganoderma was “Pharmacology & Pharmacy,” in which immunomodulation (25.60%) and cancer treatment (21.40%) were the most popular subcategories. Moreover, we have provided an overview of the bioactive components and combinatorial immunomodulatory effects for the use of Ganoderma in the treatment of cancer, including the major pathways of immune cells. Immunomodulatory protein and polysaccharides are the key bioactive factors responsible for cancer immunotherapy, and the NF-κB and MAPK pathways are the most comprehensively investigated major pathways. Our results indicate that Ganoderma has a broad-spectrum application for the treatment of cancer through the regulation of the immune system. This review provides guidance for future research into the role of Ganoderma in cancer immunotherapy.

Health Benefits of Ganoderma lucidum as a Medicinal Mushroom

“…Triterpenoids of G. lucidum have been reported to have many enzyme inhibitory activities that are useful as chemotherapeutic agents. Moreover, G. lucidum polysaccharides and triterpenes have immunomodulating, immunostimulating, anti-inflammatory, anti-oxidant, and radio-protective activities related to cancer (Dinesh Babu and Subhasree, 2008;Wachtel-Galor et al, 2011;Xu et al, 2011b;Wiater et al, 2012;Boh, 2013;Kao et al, 2013;Zhang et al, 2007;Zhou et al, 2012;Cheng and Sliva, 2015;Duru and Tel Çayan, 2015;Ferreira et al, 2015;Valverde et al, 2015;Cao et al, 2018;Cör et al, 2018;Sohretoglu and Huang, 2018;Sudheer et al, 2018;Ye, 2018). Liu et al (2007) isolated a compound (Ganoderol B) from the fruiting body of G. lucidum and showed its anti-androgen effect against prostate cancer.…”

“…Within the anticancer and antimetastatic activities, NF-κB and MAPK, the most comprehensively investigated major pathways were shown to be activated and released cytokines that subsequently inhibited the growth of tumor cells. In addition, TLR-4 was an effective receptor involved in the host defense mechanism of the immune response to polysaccharides (Deepalakshmi and Mirunalini, 2011;Boh, 2013;Kao et al, 2013;Cheng and Sliva, 2015;Cao et al, 2018;Sohretoglu and Huang, 2018). In addition, other active compounds from G. lucidum have been described, such as ergostane sterols and ergosterol (provitamin D2; range, 189.1-1453.3 μg/g), nucleosides, and nucleotides (T, U, I, A and G; 303-1217 μg/g in the mushroom cap and 22-334 μg/g in the stem) with platelet aggregation effect, fatty acids (palmitic acid, linoleic acid, oleic acid, stearic acid) with potential effect of tumour cell proliferation inhibition, and fatty acids (nonadecanoic acid, heptadecanoic acid, stearic acid, palmitic acid) with inhibitory activity, alkaloids (choline, betaine, saponin, flavonoid, tannin), vitamins (riboflavin, vitamin C), essential and nonessential minerals (selenium (Se) up to 72 μg/g dw; germanium (Ge) 489 μg/g, Cu, Zn, P), hydrocarbons, monoterpenes, and sesquiterpenes (Paterson, 2006;Wachtel-Galor et al, 2011;Boh, 2013;Cör et al, 2018;Sudheer et al, 2018).…”

“…Table 1 shows the common pharmacological effects of major bio compounds and various extracts of G. lucidum. Zhou et al, 2007Zhou et al, , 2012Wachtel-Galor et al, 2011;Xu et al, 2011a;Boh, 2013;Cao et al, 2018;Sudheer et al, 2018 Sanodiya et al, 2009;Stojkovic et al, 2014;Bal, 2019;Hleba et al, 2014 Ganoderma presents three characteristics for prevention or treatment of diseases: (1) it does not produce any toxicity or side effects; (2) it does not act on a specific organ and (3) it promotes the improvement of normalization of the organ function (Valverde et al, 2015). Because of its biologically active compounds, modern pharmacological tests have generally demonstrated some important pharmacological effects of G. lucidum such as anxiolytic, anti-angiogenic, antidepressant, antitumor, anticancer, cytotoxic, antimetastatic, hypoglycemic, antihyperlipidemic, antihistaminic, anti-obesity, anti-inflammatory, antihypertensive, anti-allergic, antihistaminic, antiradiation, hepatoprotective, chemopreventive, immunomodulating, anti-anemic, anti-androgenic, antimutagenic, antioxidant, antiparasitic, antihepatitis, anti-aging, anti-androgenic, anti-arthritic, antidiabetic, antibacterial, antiviral anti-HIV, prebiotic, neuro-protective, dermatocosmetic, acetylcholinesterase inhibitory, acute gastric ulcer mucoprotective, cytokine production inductive, inhibition of lipid peroxidation/oxidative DNA damage, maintenance of gut health, stimulation of probiotic, urinary tract in men, atherosclerosis, liver and kidney protective, cardiovascular potential activities in addition to other activities against such as fibromyalgia in women, platelet aggregation, and topical sarcoidosis (Zhou et al, 2012;Sanodiya et al, 2009;Deepalakshmi and Mirunalini, 2011;Wachtel-Galor et al, 2011;Boh, 2013;Bishop et al, 2015;Duru and Tel Çayan, 2015;Ferreira et al, 2015;Valverde et al, 2015;Cör et al, 2018;Hapuarachchi et al, 2016aHapuarachchi et al, , b, 2017Hapuarachchi et al, , 2018Khatian and Aslam, 2018;…”

“…In addition to various in vitro and in vivo studies previously conducted on therapeutic and medicinal properties of G. lucidum (Gao et al, 2005;Wachtel-Galor et al, 2011;Boh, 2013;Hapuarachchi et al, 2016aHapuarachchi et al, , b, 2017Hapuarachchi et al, , 2018Cao et al, 2018;Cör et al, 2018;Khatian and Aslam, 2018;Sudheer et al, 2018;Zeng et al, 2018), the pharmacological effectiveness of G. lucidum and its extracts, drugs, spores, tablets, capsules etc. have confirmed and proved by clinical trials, mostly in Asian countries, such as China, Japan, and Korea in addition to USA and Malaysia (Wachtel-Galor et al, 2011;Boh, 2013;Nahata, 2013;Cheng and Sliva, 2015;Hapuarachchi et al, 2016a, b;Cao et al, 2018;Cör et al, 2018;Sohretoglu and Huang, 2018;Sudheer et al, 2018;Zeng et al, 2018;Sharma et al, 2019;Zhao et al, 2019). However, due to the difficulty in obtaining large amounts of the pure triterpenoids and polysaccharides, double-blind clinical data of the active components are limited.…”

Bioprospecting of the agaricomycete Ganoderma australe GPC191 as novel source for l-asparaginase production

“…In case of cancer therapy, besides reduction of their effectiveness due to the resistance from cancer cells, the extensive use of chemical drugs has led to reduction of quality of life of patients in general. Ganoderma , often considered as an herbal fungus, is frequently administered in combination with drugs for cancer and has been an effective immunotherapeutic agent towards several types of cancer such as liver, leukaemia, lung, and breast cancer 14 .…”