Anticancer Mechanisms of Ginsenoside Compound K: A Review

Abstract

Cancer, also known as malignant tumors, is formed due to abnormal mutations and the proliferation of human cells. Cancer cells not only demonstrate accelerated proliferation but also show robust invasive and metastatic potential, disseminating from a primary affected region of the body to multiple areas and potentially culminating in organ dysfunction or failure, thereby jeopardizing the individual's life. The rapid growth of the biopharmaceutical market has given rise to numerous novel medicines, thereby precipitating a paradigm shift in contemporary drug development methodologies. This modification is focused on identifying methodologies that can effectively target cancerous cells while minimizing damage to normal cells. There is an increasing societal movement that supports the utilization of natural ingredients derived from plants. In recent years, traditional herbal medicine has experienced a surge in popularity within the global cancer market. In comparison with the use of more toxic chemotherapy methods, there has been an increasing focus on advanced therapies that exhibit reduced side effects. Ginsenoside compound K (CK) is derived from the natural components in ginseng through biotransformation. The utilization of CK in cancer research is a practice engaged in by numerous scientists. The underlying rationale is that CK exhibits a multitude of effects within the realm of cancer research, including but not limited to the mitigation of inflammation, the suppression of cancerous cell proliferation, and the safeguarding of cardiovascular, hepatic, and renal functions. This review methodically identifies and organizes CK-related journals according to the following key points of cancer treatment: the effects on cancer cells themselves, angiogenesis inhibition, modulation of immune response to identify cancer cells, and inflammation regulation. The intricate interplay between ginsenoside CK and cells is elucidated through a graphical representation. The present review focuses on the results of CK in in vitro tests. It is our hope that the present article will aid future studies on the results of CK in vivo tests, clarify the correlation between cellular mechanisms in vivo and in vitro tests, and assist in the development of drugs.

Keywords: angiogenesis; cancer; chronic inflammation; ginsenoside compound K; stromal cell-derived factor 1.

Figure 1

Stereochemical structures of dammarane-type diol and triol ginsenosides. Dammarane has the molecular formula C₃₀H₅₄ and is a type of tetracyclic triterpene.

Figure 2

Different glycosyl combinations in ginsenoside structures (including xylose, rhamnose, glucose, arabinofuranose, and arabinopyranose).

Figure 3

The chemical structure of ginsenoside compound K (CK).

Figure 4

Ginsenoside CK inhibits the expression of AKT/mTOR/p70S6K1 proteins and blocks the PI3K/AKT/mTOR signaling pathway in cancer cells, reducing the expression of MMP2 and MMP9 proteases. This results in the inhibition of cancer cell proliferation and invasion.

Figure 5

Ginsenoside CK reduces the binding of SDF-1 to CXCR4, thereby inhibiting the activation of PKC-α and ERK, resulting in a decreased expression of MMP2 and MMP9 proteases downstream in the signaling pathway.

Figure 6

Ginsenoside CK can inhibit the p38 and AKT signaling pathways downstream of PI3K in endothelial cells, blocking angiogenesis near cancer tissues.

Figure 7

Ginsenoside CK inhibits the activity of telomerase reverse transcriptase and telomerase in cancer cells, shortening telomere length and halting cell division, inducing apoptosis.

Figure 8

Ginsenoside CK can inhibit the inflammatory response induced by lipopolysaccharides, reduce the expression levels of ERK and JNK, and decrease the production of inflammation causing NO and PGE2.

Figure 9

Ginsenoside CK can enhance the expression of CD69, CD80, and CD86, stimulate the NF-κB and AP-1 inflammatory signaling pathway, and induce macrophages to secrete iNOS and TNF-α to enhance inflammatory response. Conversely, CK can also inhibit the expression of CD82 protein, reducing monocyte differentiation into macrophages to avoid excessive inflammatory responses.

Figure 10

Ginsenoside CK can inhibit the activity of AKT1 in cancer cells, increase the expression of apoptotic proteases Caspase-3, Caspase-8, and Caspase-9, thereby inducing cancer cell apoptosis. Additionally, it also suppresses the migration and invasion of cancer cells.

Figure 11

Ginsenoside CK enhances the concentration of mitochondrial ROS in cancer cells, leading to a loss in mitochondria membrane potential and increased expression of Bax, Caspase-3, and Caspase-9, while decreasing the expression of Bcl-2, thus inducing apoptosis in cancer cells.

Figure 12

Ginsenoside CK can induce autophagy in cancer cells by increasing ROS concentration. It can also enhance the expression of tumor suppressor gene p53 and CHOP protein, promoting the expression of DR5, thereby increasing the sensitivity of cancer cells to TRAIL. This further induces apoptosis signaling, ultimately resulting in cancer cell death.

Figure 13

Ginsenoside CK can block the binding of T cell PD-1 with cancer cell PD-L1, preventing cancer cells from evading immune system surveillance and enhancing T cell recognition of cancer cells.