Most deaths associated with lung cancer are due to the migration of cancer cells to other organs—a process called metastasis. Although cancer therapies have advanced, treatments for lung cancer metastasis continue to lag.

The root of red ginseng (Panax ginseng) has been used as food and herbal medicine for thousands of years globally and especially in Korea and China, owing to its medicinal properties. However, the composition and activities of red ginseng vary depending on the processing method. Recent studies have shown the efficacy of red ginseng against lung cancer metastasis.

Red Ginseng
KMxG red ginseng manufactured through microwave processing [Korea Institute of Science and Technology (KIST)]

A new study conducted by scientists at the Korea Institute of Science and Technology (KIST) reports the successful use of a microwave processing method for ginseng that increases trace amounts of Rk1 and Rg5 ginsenosides—a class of natural steroid sugars found almost exclusively in plants of the genus Panax—that effectively inhibit the metastasis of lung cancer.

These findings are published in the article, “Ginsenosides Rk1 and Rg5 inhibit transforming growth factor-b1-induced epithelial mesenchymal transition and suppress migration, invasion, anoikis resistance, and development of stem like features in lung cancer” in the Journal of Ginseng Research and are the result of a collaborative study conducted by research groups led by Jungyeob Ham, PhD, from the Natural Product Research Center at the KIST Gangneung Institute of Natural Products and Hyeonseok Ko, PhD, at the Seoul Asan Medical Center.

Jungyeob Ham
Jungyeob Ham, PhD, from the Natural Product Research Center, KIST

“Although components of red ginseng previously have been shown to kill cancer cells, this study proved that these components of red ginseng have other anti-cancer effects and can inhibit lung cancer metastasis. This provides scientific evidence that may lead to the future development of anti-cancer drugs derived from natural products,” says Ham.

Cancer metastasis is a multistep process starting with stationary cells becoming motile and invasive. This change, technically termed the epithelial to mesenchymal transition or EMT, is accompanied by changes in the shape of cancer cells and a decrease in their adhesiveness to cells around them. The expression of adhesive proteins such as E-cadherin, decreases in cancer cells and the invading cells override the protective programming of cell death in the event of cellular aberrations.

Transforming growth factor-beta1 (TGF-b1)—a secreted cytokine signaling protein—that suppresses cell growth, differentiation, and death, is particularly important in EMT.

The new microwave processing method for red ginseng is based on the same principle as a microwave oven. Compared to existing ginseng processing methods such as repetitive steaming and drying, microwave processing increases the concentration of the three main active components, Rg3, Rk1, and Rg5, more than 20 times, the authors demonstrate.

The team has shown in earlier studies that red ginseng produced by this microwave processing method, which they call KMxG, is effective against prostate, cervical, and skin cancers, and protects against drug-induced kidney damage.

“Because we can control the active ingredient contents of red ginseng by using microwave processing methods like the one that produced KMxG, it may be possible to develop customized functional materials for various diseases,” says Ham.

The researchers treated lung cancer cells with Rk1 and Rg5, the main components of KMxG red ginseng extract, and showed that both components effectively inhibited various processes related to cancer metastasis induced by TGF-b1.

Specifically, the authors show treatment with Rk1 and Rg5 suppressed EMT induced by TGF- b1 in A549 lung cancer cell lines and the expression of stem cell markers, in a dose-dependent manner. The authors also show that Rk1 and Rg5 markedly suppressed TGF-b1-induced metalloproteinase-activity that can degrade the matrix of connective tissue around cells, promoting the invasiveness of cancer cells.

Schema
A schematic diagram of the inhibition of lung cancer metastasis by ginsenoside Rk1 and Rg5.[Korea Institute of Science and Technology (KIST)]

The microwave processing technology developed by the team was transferred to Ponin Bio Co., Ltd. in 2020 for a technology fee of KRW 800 million and is currently being developed for commercialization.