Exploring Ganoderma Lucidum Polysaccharides:

A Potent Anti-Cancer Agent

Yanzhen Wang

Shanghai Starriver Bilingual School, Shanghai, 200000, China

Keywords: GLP, Cancer, Anticancer Effect.

Abstract: The article will focus on introducing Ganoderma lucidum, a mushroom that may be beneficial to

humans. In the eyes of most people, Ganoderma lucidum is simply a traditional Chinese medicine

with the function of calming people’s mind and relieving the cough. In recent years, under the

implementation of various experiments, however, scientists have gradually discovered the efficacy

of Ganoderma lucidum in assisting in the treatment of cancer, so this fungus has quickly attracted

people's attention. After extracting and analysing the internal substances of Ganoderma lucidum,

scientists found that the Ganoderma lucidum polysaccharide (GLP) contained in it is one of the

key components that enable Ganoderma lucidum to produce anti-cancer properties. In this article,

some studies that are relevant to GLP are summarized, and the relevant experimental data collected

from the internet are provided to demonstrate its pro-apoptotic and anti-proliferative effects on the

cells.

1 INTRODUCTION

Ganoderma lucidum, which people commonly called

Linzhi or Reishi, is a mushroom that has immerse

health benefits in China, and is a traditional Chinese

medicine that Chinese people often use it in their

daily lives. As the famous Chinese herbal word says,

“ Ganoderma lucidum has a rich range of

pharmacological components, including the

components like polysaccharides, furans, alcohols,

nucleosides, alkaloids, triterpenes, oils, various

amino acids and proteins, enzymes, organic

compounds, and various trace elements. ” This

fungus was found to have the effect of helping the

human body in ancient, and it has also attracted

significant attention in recent years due to its reported

anti-cancer properties, which scientists have just

found out. After extracting and purifying the

Ganoderma lucidum, scientists found that one of the

key components that results in the anticancer effect of

the Ganoderma lucidum is the Ganoderma lucidum

polysaccharides, which is often called GLP. It exists

in the fruiting bodies and the mycelium of the

Ganoderma lucidum. After a series of experiments

and operations, scientists prove that these

components have significant anticancer potential

effects to cancer cells through various mechanisms

such as immunomodulation, anti-proliferation, pro-

apoptosis, anti-metastasis, and anti-angiogenesis

(Sohretoglu and Huang, 2018). In the early years,

some scholars have proved that Ganoderma lucidum

mycelium has a significant inhibitory effect on

myofiber malignant tumors in mice, and also has an

inhibitory effect on lung metastases. Intragastric

administration of sarcoma mice could significantly

inhibit the growth of sarcoma, and showed a dose-

response relationship. Experiments have also been

shown to significantly promote the expression of

tumor necrosis factor in mouse macrophages,

increase the production of TNF, and thus kill tumor

cells. Ganoderma lucidum Fukangbao also has the

effect of inhibiting tumor growth, and it has been

found to have an inducing effect on interleukins in

tumor-bearing mice, indicating that the drug exerts an

inhibitory effect on tumors by regulating the host's

biological response modulator system. Ganoderma

lucidum decoction can significantly reduce the tumor

weight and significantly reduce the activities of tumor

marker enzymes glutamyl glycosyl-transferase and

R-glutamphthalein transdermase in mice with ascites

in charge of liver carcinoma, improve the killing

power of macrophages to tumor cells, enhance the

Wang, Y.

Exploring Ganoderma Lucidum Polysaccharides: A Potent Anti-Cancer Agent.

DOI: 10.5220/0013933000004914

Paper published under CC license (CC BY-NC-ND 4.0)

In Proceedings of the 2nd International Conference on Renewable Energy and Ecosystem (ICREE 2024), pages 303-307

ISBN: 978-989-758-776-4

303

proliferation of splenocytes, and thus inhibit tumor

growth. The above studies have shown that a variety

of preparations of Ganoderma lucidum have anti-

tumor effects.

It is of vital importance to focus on the study of

the function of GLP, as it has the ability to inhibit the

proliferation of various cancer cells. As a new type of

drug, Ganoderma lucidum has high research value, so

the scientists increased their efforts on it, and they

carried various of related experiments to study the

efficiency. In this article, a series of experiments on

studying the impact of GLP on the treatment of

tumours are displayed, the relevant experimental data

collected from the internet are also provided to

demonstrate the Ganoderma lucidum ’ s anti-

proliferative and pro-apoptotic effects on the cells.

The experiments have demonstrated that GLP

inhibits the growth of various of cancer cells in mice

body, rats’ adrenal medulla pheochromocytoma cells,

human bladder cancer cells, and human colon cancer

cells. As Ganoderma lucidum has shown significant

inhibitory effects on the growth of various cancer

cells, scientists generally believe that GLP has effects

on the treatment of cancer, and they conducted

several relevant experiments to further analyse the

effect of GLP on the tumour cells. In this article, three

typical articles are selected for analysis, and accurate

conclusions are made based on the experimental data

(Ma et al, 2023).

In addition to that, the anticancer effects of GLP

can also be shown through various of pathways,

including AKT and MAPK signalling pathway.

These pathways all play crucial roles in mediating the

effects of GLP. In the first example, how GLP affects

the cancer cells is explained by modulating the eIF4e

pathway and displaying the whole process, and it

shows that GLP can effectively hinder tumour cell

proliferation, promote apoptosis, and make it a

valuable compound for exploring new cancer

treatments.

In the experiment that use the human colon cancer

cells, GLP has been shown to reduce cell viability in

a concentration-dependent manner. Moreover, related

to the experiment 2 in the article, GLP also induces

apoptosis by preventing cancer’s mechanisms; GLP

can enhance the release of lactate dehydrogenase

(LDH), increase intracellular Ca2+ levels. These

findings all emphasize the multifaceted ways that

GLP can exerts its anticancer effects, providing a rich

area for further investigation and therapeutic

development.

In the example 3, the effects of Ganoderma

lucidum polysaccharides on tumour growth is

discussed by giving the experiment about using the

cyclophosphamide-treated mouse cancer cells. In the

experiment, scientists examined the alleviation of the

cyclophosphamide induced immunodepression, and

they also evaluated anti-metastatic effects of

Ganoderma lucidum in cyclophosphamide -treated

cells by giving and comparing specific experiment

data. While the preliminary results are encouraging,

before further research can consolidate its efficacy

and safety, caution must be maintained when using

the Ganoderma lucidum. Like any medicinal

substance, Ganoderma lucidum may pose certain

risks or interactions with existing treatments, though

there are currently no relevant reports about the risk

of using Ganoderma lucidum (Ge et al, 2023).

Moreover, the possibility of Ganoderma

lucidum's effects being attributed to a placebo

response cannot be dismissed. Placebo effects, driven

by psychological factors, can sometimes lead to

effective improvements in outcomes. Therefore,

rigorous clinical trials are still necessary to

differentiate between genuine therapeutic benefits

and placebo effects associated with Ganoderma

lucidum consumption. Although more researches are

needed to fully understand the whole mechanism and

potential drawbacks of Ganoderma lucidum, the field

of natural medicine has broad prospects for future

medical development. The continuous exploration

has paved the way for innovative cancer therapies and

new treatment methods.

In conclusion, while Ganoderma lucidum shows

immense potential in the fight against cancer,

comprehensive research efforts are indispensable to

validate its efficacy, safety, and optimal usage. The

development of medicinal fungal researches,

especially those experiments about Ganoderma

lucidum, allow us to glimpse the future where natural

compounds plays a crucial role in the next generation

of cancer treatment.

2 MECHANISM

GLP functions in various ways. It could activate and

enhance the function of cytotoxic T cells that can

directly attack the tumour to death; it promotes the

activation of dendritic cells, hence initiating the

immune responses against cancer and secreting

antigens to T cells; it could stimulate B cell ’ s

activity, leading to increased production of antibodies

that can target cancer cells; it can enhance the activity

of the natural killer cells (NK), which play an

important role in detecting and destroying cancer

cells; it can help to enhance the macrophage function

of the cells and increase cells’ ability to engulf, and

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finally eliminate the cancer cells. Through

modulating these cells that have the immunity,

Ganoderma lucidum polysaccharides can potentially

enhance the overall immune response against cancer,

helping the body's ability to effectively identify and

destroy the cancer cells.

2.1 The Anti-Cancer Effects in Breast

Cancer Cells

GLP reduces the expression of some signalling

molecules, which may affect the spread of breast

cancer in the body. Eukaryotic initiation factor 4E

(eIF4E) can form eIF4F complexes with eIF4A and

eIF4G to participate in the initiation of eukaryotic

translation. Therefore, by binding to the cap structure

at the 5 'end of mRNA, eIF4E can bring eIF4A to the

5' end of mRNA, allowing eIF4A to exert helicase

activity to open the secondary structure at the 5 'end

of mRNA. eIF4E is an oncogenic gene in various

cancers, promoting cancer growth and proliferation.

It may be a potential therapeutic target for cancer and

a biological indicator for prognostic evaluation; The

application of eIF4E inhibitors may provide a new

approach for cancer chemotherapy. Phosphorylation

can regulate the activity of eIF4E. For instance,

phosphorylation of serine at position 209 of

mammalian eIF4E can enhance the binding of eIF4E

to capped mRNA and stabilize the interaction

between eIF4E and eIF4G.] In the experiment, to

examine whether Reishi treatment can affect the gene

expression through pathways such as

PI3K/AKT/mTOR, PI3K/AKT signal RT2 Profiler

PCR array was used in SUM-149 cells. After treating

them with the carrier and/or the 0.5mg/mL

concentration Reishi solution provided in the

experiment for about 3 hours, the experiment begins.

Methods such as Real Time RT-PCR Analysis,

Western Blot Analysis, Metabolic Labeling, Cap

Binding Assay, Immunohistochemistry, and

Statistical Analysis are being used during the process

to get the data and to compare the results from these

experiments (Rong, 2020).

Immunohistochemistry is a technique used to

visualize the distribution of specific proteins or

antigens in tissue samples. The method relies on the

use of antibodies that bind to target proteins within

cells or tissues, allowing them to be detected and

localized. The binding of these antibodies to target

proteins can be visualized under the special

microscope, providing valuable information about the

distribution of the protein within the sample, and the

data can be collected. Immunohistochemistry is

commonly used in research and diagnostic settings to

study various diseases, understand cell function, and

evaluate biomarker expression patterns in different

tissues. It is a powerful tool for studying protein

localization, identifying disease markers, and

elucidating biological processes at the tissue level.

Ganoderma lucidum reduces the expression of

these pathways’ genes and mTORC1 effectors. The

panel shows the gene expression effects by

comparing data by dividing time into three parts.

Down-regulated genes are on the left side of the row,

while up-regulated genes are on the right side of the

row. And the statistically significant genes are higher

than the P<0.05 line. In panel B, the proteins are the

same for each sample, with different lanes (tumour

lysate from mice under vehicle or Ganoderma

lucidum) showing different reflectance. Both of the

panel show the effectiveness of the expression of the

Ganoderma lucidum, which directly indicates that

Ganoderma lucidum can help to reduce the signalling

pathways during the process. Quantification was

done, and the results showed that Ganoderma can

significantly reduce the expression of key IBC

proteins in vivo (Wei, 2021).

Tumours treated with Ganoderma in picture E

above the text showed smaller size and lower Ki-67

and Vimentin levels compared to vehicle-treated

mice, which may indicate reduced cell proliferation

and stromal characteristics. These findings are

consistent with the decrease in mTOR activity in

Ganoderma-treated cancer cells. The study

demonstrates that Reishi treatment in mice leads to

significant reductions in tumour growth and weight.

This effect is associated with decreased expression of

key molecules in the signalling pathways mentioned

above at both protein and gene levels, particularly

affecting mTOR activity. Additionally, the research

reveals concurrent downregulation of E-cadherin and

p120-catenin along with reduced levels of eIF4G,

supporting and expanding upon prior discoveries. In

conclusion, the Ganoderma lucidum reduces tumour

growth, weight, and it is also helpful to the

proliferative of the marker expression. So, maybe,

Ganoderma lucidum extract can be used as an

anticancer therapeutic for the patients.

2.2 The Anti-Cancer Effects in Colon

Cancer Cells

HCT-116 cell line is a test model to help to

understand the hypothesis that GLP can influence the

anticancer effects in this experiment. Researchers

have found that GLP can reduce the cell viability of

human colon cancer cells. As the concentration

increases, the cell viability decreases. GLP induces

Exploring Ganoderma Lucidum Polysaccharides: A Potent Anti-Cancer Agent

305

apoptosis by increasing the concentration of LDH and

promoting Ca2+ levels in the cells, thereby activating

JNK pathways. Ganoderma lucidum that is obtained

from the basidiomycete fungal extracts has shown

significantly inhibition on various kinds of cancer

cells, including the colorectal cancer that this part

mentioned. GLP, in vivo and in vitro, exerts the

cytotoxic and anti-angiogenic to influence the tumour

cells. Before the experiment, cells were treated with

5 mg/mL GLP for different time: 0h, 12h, 24h, 36h

and 48 hours). After washing 3 times with PBS, cells

were lysed in RIPA lysis buffer, and they were put on

the ice for thirty minutes.

The study investigated the effect of GLP on HCT-

116 cell viability, and it shows that GLP exhibits

significant inhibitory effects on cell viability. The

50% inhibitory concentrations at 24h, 48h and 72

hours were 9.25, 5.72 and 3.69 mg/mL. The

inhibitory activity of GLP lasts for at least 72 hours.

Starch control experiments showed a dose-dependent

decrease in cell growth, whereas 5 fluorouracil

significantly inhibited cell viability. Significant

changes have appeared in the cells that are treated

with GLP, including the change of its shape, the

decreasing of its volume, and the decreasing of the

concentration-dependent cell numbers (Wang et al.,

2018).

compared with the control group, a GLP solution

with a concentration of 5 mg/mL significantly

increased the activity of caspase-8. The results

indicate that the activation of the caspase dependent

apoptotic signalling pathway may involve the GLP

induced apoptosis of human colon cancer cells. The

presence of GLP provokes the activation of caspase-

8 and enhances the expression of caspase-3,

indicating that GLP induced cell death involves a

caspase-dependent pathway. It also increased the

abundance of Fas protein. By administering GLP

treatment, the signal transduction of active caspase-8

was significantly increased, while the levels of Fas

protein and caspase-3 were elevated.

In conclusion, this experiment introduces a new

way on how GLP affects human colon cancer cells by

stimulating cell death and promoting apoptosis. These

results highlight the promising potential of GLP in

colon cancer prevention and treatment, opening up

avenues for further exploration in the field of

pharmacology. The findings indicate that GLP could

be a valuable candidate for developing new methods

to combat colon cancer. The combination usage of

Chinese herbal medicine and the radiotherapy can

potentially inhibit various cancers, reduce treatment

side effects, improve quality of life, and prolong the

survival of cancer patients. Preliminary studies have

shown that simultaneous treatment with GLP and 5-

fluorouracil can inhibit in vitro cultured human colon

cancer cells. Overall, experiments indicate that the

antitumor properties of GLP are attributed to its

subcomponents, particularly high molecular weight

polysaccharides. The research explores how GLP

affects human colon cancer cells by stimulating

apoptosis through the ratio and triggering the

mitochondrial intrinsic pathway, causing

mitochondrial membrane depolarization (Lin, 2015).

2.3 Effects of the Ganoderma Lucidum

that Is the Antlered Form on the

Growth and the Metastasis on the

Cyclophosphamide-Treated Mice

Cancer Cells

In this experiment, the alleviating effect of the

antlered shaped Ganoderma lucidum on

immunosuppression induced by cyclophosphamide is

examined, and the anti-tumour and anti-metastatic

effects of Ganoderma lucidum AF in

cyclophosphamide treated mice are examined. it

shows that treatment with CY caused a decrease in

the weight of C57BL/6 mice compared to the control

group at the beginning of the experiment, but the

weight began to increase starting from 4 days after the

administration. However, if the diet that has 2.5% G.

lucidum AF were given to the mice 7 days before CY

administration, the weight loss induced by CY was

inhibited by G. lucidum AF, so in most of days, the

weight of the mice that use Reishi and CY is bigger

than the weight of mice that only use CY. C57BL/6

mice were fed either a standard diet or a diet

containing 2.5% GLP AF solution for a week,

followed by an injection of 150 mg/kg of CY. Data

were collected at days 3, 5, and 7 post-injection. NK

cells activity was measured at the effector-target

ratios of 40:1 and 80:1. The results showed that NK

activity changed over time after CY administration.

Statistical differences between groups (p < 0.05) were

observed using ANOVA and Fisher's PLSD post hoc

test. Data demonstrate the potential impact of dietary

factors on NK cell function after CY treatment in this

mouse model (Lin et al., 2004). In these three groups,

the sample with the adding of CY and Reishi shows

the highest splenic NK activity rate, which also

indicates the efficiency of Reishi. Hence, from

analysing the data given above, we can get the

conclusion that the use of G. lucidum AF can improve

the effectiveness of cancer treatment by preserving

natural killer cell activity (Unlu et al., 2016 &

Ahmad, 2020).

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3 CONCLUSION

Previous studies have suggested that compounds

found in Ganoderma lucidum may have anti-tumour

properties by inhibiting the angiogenesis, which is the

process by which tumours form new blood vessels to

sustain the cancer cells’ growth. By disrupting this

process, Ganoderma lucidum can slow down or even

prevent the spreading speed of cancer cells to other

parts of the body. Additionally, some studies suggest

that Ganoderma extract may have

immunomodulatory effects, enhancing the body's

immune response against cancer cells.

From my personal perspective, Ganoderma

lucidum really has great potential in cancer treatment.

It can be found in the natural world, and it has a

relatively low toxicity compared to nowadays other

medicines. Both of these traits make the Ganoderma

lucidum as an attractive field for the further research.

Integrating Ganoderma lucidum into medical practice

could provide patients with a complementary

approach to managing cancer-related symptoms and

potentially improve treatment outcomes.

Although Ganoderma has shown potential as an

adjunct to cancer treatment, more comprehensive

clinical trials are needed to fully understand its

efficacy and safety. It will be important for scientists

to conduct further research to determine the optimal

method to use the Ganoderma lucidum. Only through

rigorous testing can the medical community

effectively incorporate Ganoderma into mainstream

cancer treatments.

In conclusion, while Ganoderma lucidum may not

be a standalone cure for cancer, its ability to inhibit

tumour growth and modulate immune responses

positions it as a valuable tool in the fight against

cancer. Continued research and clinical trials will be

essential in unlocking the full therapeutic potential of

Ganoderma lucidum and integrating it into

mainstream oncology practices. Ultimately, the

future looks bright for Ganoderma lucidum as a

complementary therapy in cancer care, offering hope

for improved patient outcomes and quality of life.

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