Ganoderma lucidum extract (GLE) impairs breast cancer stem cells by targeting the STAT3 pathway

Ganoderma lucidum extract (GLE) impairs breast cancer stem cells by targeting the STAT3 pathway

Cancer stem cells are regarded as the source of cancer occurrence, drug resistance of cancer, and even the seemingly cured cancer resurgence, metastasis and spread behind the scenes. Therefore, the number and activity of cancer stem cells are also important indicators of good treatment.

Tri-negative breast cancer is considered to be associated with cancer stem cells because it is difficult to treat. “Tri-negative” refers to the fact that there is no estrogen receptor (ER), lutein receptor (PR) and epidermal growth factor receptor (Her2) on the surface of breast cancer cells of this type, and that the cancer cells themselves will continue to grow without hormone stimulation.

Because of the lack of target receptors, traditional chemotherapy can only be used to treat triple-negative breast cancer. Once cancer cells become resistant to chemotherapeutic drugs, follow-up treatment is almost impossible. Therefore, if there is a way to suppress cancer stem cells in this type of cancer, it will be able to fight for more survival space for cancer patients.

Of course, this is not an easy task, because cancer stem cells not only have a strong ability to survive and regenerate, but also have the first-rate ability to avoid the pursuit of epidemic system and drug pursuit. Faced with such a difficult opponent, Ganoderma lucidum still seems to have its way.

A study published in Oncotarget in November 2018 by the Medical College of Central Caribbean University and New York University Medical College in the United States shows that Ganoderma lucidum extract can not only reduce the proportion of cancer stem cells in triple-negative breast cancer, but also inhibit the growth rate of these tumors in animals by oral administration.

Tumor growth was significantly inhibited after taking the Ganoderma Lucidum Extract

Researchers implanted human triple negative breast cancer cell lines with cancer stem cell characteristics into breast tissue of female mice with deficient immune system. After one week, mice were fed with Ganoderma lucidum extract at a daily dose of 28 mg/kg.

Ganoderma lucidum extract contained Ganoderma lucidum polysaccharide, Ganoderma triterpenoids and a small amount of wall-breaking spore powder. The extract was dissolved in 10% ethanol and fed to breast cancer mice (Ganoderma lucidum extract group), while the other group was fed the same ethanol solvent (solvent control group) for comparison.

After 10 weeks of treatment, whether the volume of tumors (Pic. 1) or the weight of tumors (Pic. 2), the Ganoderma lucidum extract group was significantly less than the solvent control group without Ganoderma lucidum.

Since the experimental subjects chose mice whose immune function could not function properly, the experimental results represented the inhibitory effect of Ganoderma lucidum extract itself on “triple negative breast cancer with cancer stem cell characteristics”. If Ganoderma lucidum extract can fight with the immune system, I wonder what the result will be?

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The researchers measured the weight changes of the mice every week. From the overlapping curves in Pic. 3, we can see that there was little difference in the weight of the mice between the two groups. Since the tumors in the Ganoderma lucidum extract group were significantly larger and heavier, it can be inferred that Ganoderma lucidum extract could make breast cancer mice more “fleshy”.

 

 

 

 

 

 

 

 

 

 

 

 

When the human triple negative breast cancer cell line (MDA-MB-231) with cancer stem cell characteristics was cultured in vitro with Ganoderma lucidum extract for 24 hours, we can see that with the increase of Ganoderma lucidum extract concentration, the survival rate of cancer cells decreased , and the proportion of cancer stem cells also decreased by about half .

Meanwhile, multiple proteins secreted by cancer stem cells (OCT4, NANOG, SOX2) were also greatly reduced, and ALDH1 activity was also significantly reduced. They are all weapons that cancer stem cells use to enhance their differentiation, metastasis, invasion or tumor growth. Without their blessing, cancer stem cells would be less destructive.

In addition, the team’s study also found that the ability of human triple-negative breast cancer cell lines, MDA-MB-231 or SUM-149, to form mammosphere was significantly inhibited after treatment with Ganoderma lucidum extracts (Fig. 6).

The formation of spheroids is what breast cancer stem cells do. Normally, breast cancer cells do not have this ability. Therefore, the results of this experiment show that Ganoderma lucidum extract can indeed weaken the ability of cancer stem cells.

The study further found that Ganoderma lucidum extract mainly suppresses cancer stem cells by reducing STAT3 gene expression in cancer cells.

Reference:

Rios-Fuller TJ, et al. Ganodermalucidum extract (GLE) impairs breast cancer stem cells by targeting the STAT3 pathway.Oncotarget.  2018 Nov 13; 9 (89): 35907-35921.

2019-05-09