Scientific research has demonstrated that Ganoderma lucidum has anti-tumor effects for 50 years, and its “polysaccharides” and “triterpenes” work in a similar way.

The discovery of Lingzhi's anti-tumor effects

Do you know when science first proved that reishi mushrooms can fight tumors? It was 50 years ago.

In April 1968, the National Cancer Center Research Institute in Japan published in Gann: Japanese Journal of Cancer Research—the journal of the Japanese Cancer Society—the first-ever research report demonstrating that Ganoderma lucidum can exert an anti-tumor effect.

The team first implanted S180 cancer cells into mice, then administered Ganoderma lucidum ( Ganoderma applanatum The hot-water extract of the fruiting bodies was administered to mice via intraperitoneal injection at a dose of 200 mg per kilogram of body weight daily for 10 consecutive days. After that, the mice were fed under normal conditions until the end of the 5th week of the experiment.

The results showed that, compared to the 10 control mice that received no Ganoderma lucidum, all of whom developed tumors, half of the 10 mice that were given Ganoderma lucidum did not develop tumors.

If calculated based on the weight of the tumors that grew, the average tumor weight in the Ganoderma lucidum group was 64.9% lower than that in the control group, indicating that this Ganoderma lucidum mixture—which contains a variety of compounds soluble in hot water—exerts at least a 60% inhibition rate against tumors.

The discovery of ganoderma polysaccharides as anti-tumor agents

Three years later (in 1971), the National Cancer Center Institute in Japan published in the "Chemical and Pharmaceutical Bulletin," published by the Pharmaceutical Society of Japan, the first academic report demonstrating that "Ganoderma polysaccharides" can exert an anti-tumor effect.

They first filtered a crude polysaccharide extract (containing a variety of polysaccharides) from the aqueous extract of the aforementioned Ganoderma lucidum fruiting bodies. They then further isolated polysaccharides whose chemical structure features a main chain linked by β(1→3) glycosidic bonds. The same animal model as described earlier was used for the experiments (with slightly different dosages). The results showed that these polysaccharides exhibited tumor-inhibitory effects ranging from 50% to 60% (as shown in the table below).

Source: Sasaki T, et al. Chem Pharm Bull. 1971; 19(4): 821-826.

The above represents the first scientific evidence demonstrating that aqueous extracts of Ganoderma lucidum and its polysaccharides possess anti-tumor activity. Although β(1→3)-linked polysaccharides have been shown to be one of the key active components responsible for Ganoderma’s anti-tumor effects, the anti-tumor activity of the “whole aqueous extract of Ganoderma lucidum” is by no means inferior—because other components within the extract also contribute to its anti-tumor properties, with triterpenoids being among them.

The Discovery of Triterpenoids in Ganoderma lucidum with Antitumor Activity

Anyone who has ever tasted the decoction made from the fruiting bodies of Reishi mushrooms will find it hard to forget that indescribable bitter flavor.

In 1982, Takashi Kubota, an authority on organic chemistry specializing in bitter compounds found in natural products and then a professor at the Faculty of Medicine at Kinki University in Japan, reported in the journal Helvetica Chimica Acta, published by the Swiss Chemical Society, two compounds derived from Ganoderma. Ganoderma lucidum the bitter triterpenes—ganoderic A and ganoderic B.

This report provides the first scientific explanation for the bitter taste of Ganoderma lucidum and marks the first time that ganoderic acids have been formally recognized in academic circles. The following year, a team from the Natural Products Research Laboratory at the University of Louis Pasteur in France demonstrated that several types of ganoderic acids exhibit in vitro cytotoxic activity against liver cancer cells.

Subsequently, an increasing number of ganoderma triterpenes have been discovered, and more and more in vitro experiments have demonstrated that these compounds possess anti-tumor properties.

Ultimately, after entering the body, how much inhibitory effect can the total triterpenes from Ganoderma lucidum—containing various triterpene molecules—exert on tumors? As an example here, let’s take the report published in 2013 by the Jiangsu Branch of the China Academy of Traditional Chinese Medicine:

First, lung cancer cells are implanted into the mice, and then, starting the day after, the mice are fed Reishi mushrooms. Ganoderma lucidum The total triterpene extract from the fruiting bodies (containing ganoderic acids A, B, C1, C2, C6, and G; ganoderic acid dilute A and D; and lucidic acid A), at doses of 30, 60, or 120 mg per kilogram of body weight daily, resulted in tumor inhibition rates of 38.0%, 48.2%, and 63.4%, respectively, after 14 days. There was a clear inverse relationship between tumor size and triterpene dosage.

[Note] The “model group” refers to tumor-bearing mice that received no treatment, while the “cyclophosphamide group” refers to tumor-bearing mice that were administered chemotherapy. (Source: Molecules. 2013 Aug 19;18(8):9966-81.)

Why Ganoderma polysaccharides? 、 Can triterpenes fight cancer?

For the past 50 years, the scientific community has never ceased exploring the anti-tumor effects of Ganoderma lucidum. Thanks to the collaborative efforts of researchers from different countries and laboratories, the truth has become increasingly clear through ongoing debate and discussion.

In November of this year (2018), at the 9th International Conference on Mushroom Biology and Products held in Shanghai, Dr. Hua Fan from the Free University of Berlin in Germany presented a report titled “Exploring the Healthcare Potential of Ganoderma lucidum,” in which he analyzed the anticancer mechanisms of ganoderma polysaccharides and ganoderma triterpenes.

The team sourced reishi mushrooms ( Ganoderma lucidum A macromolecular polysaccharide named GLIS, with a β(1→3)-linked main chain and containing 8% to 9% protein components, was isolated and purified from the fruiting bodies. It was found that GLIS can enhance the cytotoxic activity of macrophages against cancer cells by activating macrophages, promoting their secretion of substances with cytotoxic effects, and boosting their phagocytic capacity.

In addition, this ganoderma polysaccharide also promotes the proliferation of lymphocytes (including T cells and B cells), activates B cells, and enhances B cell antibody secretion, thereby boosting the immune system's anti-cancer capabilities.

When GLIS was actually injected into mice previously inoculated with S180 sarcoma cells at a dose of 100 μg per mouse, the number of splenic cells (which contain lymphocytes) increased by nearly one-third, and tumor growth was significantly inhibited (with an inhibition rate ranging from 60% to 70%). This indicates that Ganoderma lucidum polysaccharide GLIS indeed possesses the ability to enhance the immune system's capacity to fight tumors.

In addition, Fan Hua’s team has also studied Ganoderma lucidum ( Ganoderma lucidum Eight individual triterpenoid compounds isolated from the fruiting bodies were evaluated for their anticancer activity. The results revealed that two of these triterpenoids exhibited significant inhibitory effects on the proliferation and pro-apoptotic activity against human breast cancer cells, human colorectal cancer cells, and malignant melanoma cells.

Further analysis of the mechanisms by which these two triterpenes induce cancer cell apoptosis reveals that they do so via two distinct pathways: “reducing the mitochondrial membrane potential” and “increasing mitochondrial oxidative stress,” thereby “directly” driving cancer cells to self-destruct—entirely different from the mechanism by which Ganoderma lucidum polysaccharide GLIS inhibits tumors “indirectly” through the immune system.

Dr. Hua Fan from the Free University of Berlin, Germany, at the presentation venue of the 9th International Conference on Mushroom Biology and Products. Since 1996, her research team has been exploring the healthcare potential of active ingredients in Ganoderma lucidum. (Photo by Tingyao Wu)

Dr. Fan Hua’s report, together with the efforts of scientists from around the world over the past half-century, have enabled us to gain a clearer understanding of how ganoderic polysaccharides and ganoderic triterpenes “achieve the same goal through different means” in their anti-tumor effects.

The biggest takeaway from this is that the best way to harness the anti-tumor effects of Ganoderma lucidum is to combine "Ganoderma lucidum polysaccharides with Ganoderma triterpenes." If even one of these components is omitted, the synergistic effect—achieving twice the result with half the effort—may be lost.

[References]

1. Ikekawa T, et al. Antitumor action of some basidiomycetes, especially Phellinus linteus Gann. 1968; 59:155-157.

2. Takuma Sasaki, et al. Antitumor polysaccharides from some Polyporaceae, Ganoderma applanatum (Pers.) Pat and Phellinus linteus (Berk. et Curt) Aoshima. Chem Pharm Bull. 1971; 19(4):821-826.

3. Takashi Kubota, et al. Structures of ganoderic acid and B, two new lanostane-type bitter triterpenes from Ganoderma lucidum (Fr.) KARST. Helv Chim Acta. 1982; 65:611-619.

4. Toth JO, et al. Ganoderic acid T and Z: cytotoxic triterpenes from Ganoderma lucidum (Polyporaceae). Tetrahedron Lett. 1983; 24: 1081-1084.

5. Toth JO, et al. Cytotoxic triterpenes from Ganoderma lucidum (Polyporaceae): Structures of ganoderic acids U-Z. J Chem. 1983; Synop.: 299.

6. Fen L, et al. Anti-lung cancer activity through enhancement of immunomodulation and induction of cell apoptosis of total triterpenes extracted from Ganoderma lucidum (Leyss. ex Fr.) Karst. Molecules. 2013 Aug 19;18(8):9966-81.

[About the Author / Wu Tingyao]

Having reported firsthand news about Lingzhi since 1999, he continues to do so to this day and is the author of “Lingzhi: Marvelous Beyond Words” (published by People’s Medical Publishing House in April 2017).

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