ANTI-CANCER EFFECTS OF GANODERMA LUCIDUM NEUTRAL TRITERPENES
The “Anti-Cancer Agents in Medicinal Chemistry” officially released in February 2020 published a research result of the team of Professor Li Peng from the School of Pharmacy of Fujian Medical University. The research confirmed through cell and animal experiments that the neutral triterpenes from Ganoderma lucidum can significantly inhibit the growth of colorectal cancer, and its mechanism of action is related to “promoting cancer cell apoptosis.”
Total Triterpenes = Neutral Triterpenes + Acidic Triterpenes
Since the first discovery of Ganoderma lucidum triterpenes in 1982, scientists have not only provided scientific explanations for “why Ganoderma lucidum fruiting bodies are so bitter” but also provided clues other than polysaccharides for the study of “Why Ganoderma lucidum is anti-tumor”.
Ganoderma lucidum triterpenes are a collective noun, which refers to the active ingredients in Ganoderma lucidum with terpene structure. According to their chemical structure, they can be divided into two groups: one group is “acidic triterpenes” including various ganoderic acids (acidic triterpene fraction, ATF), and the other group is “neutral triterpenes” including various ganoderiols (“neutral triterpene fraction”, NTF). When these two groups of triterpenes are combined, they are called total triterpenes.
Although there are many scientific evidences for the anti-tumor effects of Ganoderma lucidum total triterpenes and acidic triterpenes, there are few studies on the role of Ganoderma lucidum neutral triterpenes in this regard. Therefore, Professor Li Peng’s team focused on this part.
Using Ganoderma lucidum fruiting bodies (provided by Fujian Xianzhilou Biological Science and Technology Co., Ltd.) as the experimental material, the team first extracted the total triterpenes of Ganoderma lucidum from the fruiting bodies of Ganoderma lucidum with ethanol, and then further separated the neutral triterpenes and acidic triterpenes to explore their inhibitory effect on colorectal cancer.
Cell experiment: the anti-cancer effect of neutral triterpenes＞the anti-cancer effect of acidic triterpenes
The researchers separately cultured Ganoderma lucidum neutral triterpenes and acidic triterpenes with three different types of human colorectal cancer cells for 48 hours. On the whole, Ganoderma lucidum neutral triterpenes had significantly better inhibitory effects on cancer cell growth (proliferation) than Ganoderma lucidum acidic triterpenes (Figure 1).
Animal experiment: Ganoderma lucidum neutral triterpenes effectively inhibit tumor growth
The researchers further evaluated the anti-tumor effects of Ganoderma lucidum neutral triterpenes in vivo through animal experiments: First, the human colorectal cancer cell line SW620 with lymphatic metastasis ability was implanted under the skin of nude mice (immune-deficient mice). After the tumor has emerged, 250 mg/kg or 500 mg/kg of Ganoderma lucidum neutral triterpenes are given orally to the mice every day.
After 13 days of experiments, it was found that the intervention of Ganoderma lucidum neutral triterpenes can make tumors grow slower and smaller, and its inhibitory effect is comparable to that of the chemotherapy drug 5-Fu (20 mg/kg intraperitoneal injection per day), but it doesn’t cause serious weight loss like 5-Fu (Figure 2-5).
Active ingredients: at least nine kinds of triterpenes
As mentioned earlier in the article, Ganoderma lucidum neutral triterpenes are also a mixture, which contains a variety of different triterpenes. According to the researcher’s analysis, the above-mentioned neutral triterpenes of Ganoderma lucidum, which has an inhibitory effect on colorectal cancer, contain at least nine kinds of triterpenes (Figure 6).
Mechanism of action: to promote apoptosis of cancer cells
If these nine triterpenes are cultured separately with the human colorectal cancer cell line SW620 in vitro, they will be found to be more or less capable of killing cancer cells.
The researchers further explored the most representative ganoderma triterpene (ganodermanondiol) and found that it can initiate the apoptosis mechanism of cancer cells and push cancer cells from the endless altar to the abyss of death. Its effective concentration (inhibition of half of cancer cells) is 11.17 μg/mL.
This concentration has no lethality on normal cells (mouse embryonic fibroblast cell line NIH3T3), and the concentration must be increased to more than 80 μg/mL to have a significant effect (inhibit the survival of half of mouse embryonic cell lines). This means that ganodermanondiol can distinguish cancer cells from normal cells and give different “treatments”, which is completely different from the “all killing” effect of chemotherapeutic drugs on good and bad cells.
Whether these Ganoderma lucidum neutral triterpenes initiate the apoptosis mechanism of cancer cells is achieved by regulating the mitochondria in cancer cells is worthy of further investigation according to the researchers.
Li P, et al. Anti-Cancer Effects of a Neutral Triterpene Fraction from Ganoderma lucidum and its Active Constituents on SW620 Human Colorectal Cancer Cells. Anticancer Agents Med Chem. 2020; 20(2): 237-244. doi: 10.2174/1871520619666191015102442.
About the author/ Ms. Wu Tingyao
Wu Tingyao has been reporting on first-hand Ganoderma information since 1999. She is the author of Healing with Ganoderma (published in The People’s Medical Publishing House in April 2017).
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