Ginseng is a well-known traditional herbal medicine in East Asia, and ginsenosides, the main bioactive substances in ginseng, contribute predominantly to its pharmacological benefits.
Ginsenoside Rg3 is one of the best-known rare ginsenosides, and it is converted from prototype ginsenosides such as Rb1, Rb2, and Rd, using unique transformation methods.
Scientists have found that ginsenoside Rg3 exhibits prominent anticancer activity in various carcinomas, among which multidrug resistance reversal stands out.
One mechanism of action behind the antitumor effects of ginsenoside Rg3 maybe contributes to its immune-related pathways.
In recent years, immunotherapy has emerged as an antitumor treatment which is aimed to resume the immune system to fight cancer. The newly DFA-approved anticancer drugs, PD-1 inhibitors are well-known immunotherapy among medical scientists and cancer patients.
Programmed cell death 1 (PD-1) is a protein on the immune cells and lymphocytes, and tumor cells can produce a protein PD-L1 to bind to PD-1, thus shutting down the ability of immune cells to kill the tumor on its own.
PD-1 inhibitors work by blocking a protective mechanism of cancer cells and thus allow the immune system to destroy them.
Credited with brilliant immunity boost, ginsenoside Rg3 has also been found to inhibit cancer cells via immune-related pathways.
A study published in the journal Biomedicine & Pharmacotherapy indicated that ginsenoside Rg3 could work like PD-1 inhibitors to downregulate PD-L1 and resume immunity, thus reducing cisplatin resistance in lung cancer cells.
The researchers of the study examined the effects of ginsenoside Rg3 in cisplatin-resistant human lung cancer cell lines A549 and A549/DDP, finding that ginsenoside Rg3 inhibited the growth and recovered the T cells cytotoxicity to cancer cells by inhibiting the overexpression of PD-L1.
Ginsenoside Rg3 can be metabolized into more bioactive rare ginsenoside Rk1.
A recent study published in the journal Food & Function revealed that ginsenoside Rk1 induced apoptosis and downregulated the expression of PD-L1 in lung adenocarcinoma.
Ginsenoside Rk1 treatment also significantly inhibited tumor growth and had few toxic side effects on normal organs in the A549 xenograft model.
These findings indicated that ginsenoside Rg3, as well as ginsenoside Rk1, could be potential antitumor agents against lung cancer.
References:
Jiang Z, Yang Y, Yang Y, et al. Ginsenoside Rg3 attenuates cisplatin resistance in lung cancer by downregulating PD-L1 and resuming immune. Biomed Pharmacother. 2017;96:378-383. doi:10.1016/j. biopha.2017.09.129
Hu M, Yang J, Qu L, et al. Ginsenoside Rk1 induces apoptosis and downregulates the expression of PD-L1 by targeting the NF-κB pathway in lung adenocarcinoma. Food Funct. 2020;11(1):456-471. doi:10.1039/c9fo02166c