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Ginsenoside Rg3 inhibits cancer stemness

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Cancer stem cells are a small group of tricky tumor cells with strong capabilities of self-renewal and differentiation. They can promote tumor mobility and metastasis, and are stubbornly insensitive to antitumor drugs.

Tumors can relapse when cancer stem cells that are dormant with drug resistance in the first-stage cancer treatment are activated to facilitate metastasis. Therefore, killing cancer stem cells is what doctors always target in cancer treatment.

Ginsenoside Rg3 is a metabolized rare ginsenoside that has been shown to inhibit proliferation, induce apoptosis, suppress metastasis and new blood vessel formation in various types of cancer cells.

Some research focuses on investigating the effects of ginsenoside Rg3 on cancer stem cells which play a key role in cancer survival. Ginsenoside Rg3 has been found to potentially inhibit cancer stem cells.

In a study investigating whether ginsenoside Rg3 could inhibit cancer stem cells in non-small cell lung cancer (NSCLC) cells, the researchers of the study first found that ginsenoside Rg3 reduced the stemness of NSCLC cells. Excitedly, ginsenoside Rg3 still showed good inhibitory effects on stemness when used to treat osimertinib‐resistant NSCLC cells which had a stronger stemness than the parental cells.

The attenuated effects of ginsenoside Rg3 on the osimertinib resistance in NSCLC cells suggests that it could be a promising treatment for chemo-resistant lung cancer.

Another study revealed that ginsenoside Rg3 targets cancer stem cells and tumor angiogenesis to inhibit colorectal cancer progression in cell culture and animal experiments. The study was published in the International Journal of Oncology

Specifically, the researchers of the study investigated whether ginsenoside Rg3 could be used to strengthen the anticancer effects of chemotherapy drugs. They observed the coeffects of ginsenoside Rg3 and 5-Fluorouracil or oxaliplatin, two common chemotherapy drugs for colorectal cancer, finding that ginsenoside Rg3 strengthened the cytotoxicity of both drugs in colorectal cancer cells.

Moreover, ginsenoside Rg3 was found to downregulate the expression of B7-H1 and B7-H3, two proteins that are reversely associated with the overall survival of colorectal cancer patients.

The findings of both studies show that ginsenoside Rg3 exerts an inhibitory effect on tumor stemness. Also, some lab experiments have found that ginsenoside Rg3 could reduce chemotherapy resistance to strengthen antitumor efficacy. Altogether, ginsenoside Rg3 show good prospect in cancer treatment, and future research requires a deep dig into ginsenoside application.

A huge number of people have been reported to take herbal medicine to help cancer treatment, among which ginseng and ginsenosides are included. Ginsenosides have been widely used as adjuvant therapy in Asian countries. For example, China has approved ginsenoside Rg3 as a Class I new drug in traditional medicine to be used in tandem with first-line antitumor drugs in cancer treatment.

Recent studies have found that less polar ginsenosides show stronger bioactivities. Ginsenoside Rg3 can be transformed into ginsenosides Rk1 and Rg5 (100 mg of Rg5 can be prepared into about 7.5 mg of Rk1 and 15.1 mg of Rg5). The obtained ginsenosides, Rk1 and Rg5, were found to exert stronger antitumor activity than Rg3. Other less polar ginsenosides Rk2, Rk3, aPPD, etc. have also shown much stronger antitumor activity.

References:

Tan, QLin, SZeng, Y, et al. Ginsenoside Rg3 attenuates the osimertinib resistance by reducing the stemness of non‐small cell lung cancer cellsEnvironmental Toxicology 2020; 1– 9. https://doi.org/10.1002/tox.22899

Tang, Y., Zhang, Y., Zhou, J., Zhi, Q., Wu, M., Gong, F. … Li, W. (2018). Ginsenoside Rg3 targets cancer stem cells and tumor angiogenesis to inhibit colorectal cancer progression in vivo. International Journal of Oncology, 52, 127-138. https://doi.org/10.3892/ijo.2017.4183

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