Anticancer Potential of Ginseng-Derived Compounds Targeting Cancer Stem Cells
Introduction
According to the report of International Agency for Research on Cancer (IARC), there are 19.3 million new cases of malignant tumors and 10 million deaths worldwide in 2020. Malignant tumors have overtaken cardiovascular disease as the leading cause of human death. By dirt of low toxicity and potential pharmacological properties including anticancer effects, ginseng has gained much attention. The compounds derived from ginseng can sensitize cancer cells to anticancer therapy. One of the potential merits of ginseng-derived compounds lies in their targeting ability to cancer stem cells (CSCs).
About CSCs
CSCs are a specific subset of cells that possess high capabilities of self-renewal, differentiation potential, tumorigenicity and drug resistance. They are resistant to non-specific treatment methods such as chemotherapy and radiotherapy, and play a crucial role in tumor initiation, metastasis, drug resistance, and recurrence. CSCs can generate multiple types of tumor cells and are intimately engaged in the entire process of cancer development and progression.
Specifically, CSCs can interact with tumor surveillance microenvironment components to support the expansion of the tumor as the primary tumor growth mechanism. Besides, cells with stemness properties transition to invasiveness, persist, and translocate to metastatic sites while remaining quiescent. During colonization, CSCs can support the growth of metastatic tumors by evading immune surveillance and promoting the proliferation of quiescent CSCs.
About ginseng-derived compounds
Physiologically active compounds derived from ginseng can be categorized into ginseng saponin (e.g., ginsenosides) and non-saponin compounds (e.g., polysaccharides, peptides, polyacetylenes, phenolic compounds, terpenes, and fatty acids). Among them, ginsenosides are the most extensively researched bioactive compounds due to their distinctive presence in Panax ginseng. They can be further categorized according to the structure of their genin (aglycon): the four-ring dammarane family and the oleanane family, with protopanaxadiols (e.g., Rb1, Rb2, Rg3, Rh2 and Rh3) and protopanaxatriols (e.g., Rg1, Rg2, and Rh1) being the main functional categories within the dammarane family.CSC-targeting activity of ginseng-derived compounds with known mechanisms
Ginseng-derived compounds can modulate CSC-related signaling pathways and reduce the CSC population. Currently, the known signaling pathways of ginseng-derived compounds, such as Wnt/β-catenin, Notch, Hh, NF-κB, JAK-STAT, and PI3K/Akt pathways, have been proven to participate in regulation of CSCs.
For instance, in ginseng saponin compounds, Rg3 can inhibit the Wnt/β-catenin pathway to hamper the viability and self-renewal of patient-derived GBM stem cells. Rh2 can repress CSC in skin squamous cell carcinoma through affecting the crosstalk between autophagy and β-catenin pathway. In non-saponin compounds, panaxynol can hinder the progression of lung cancer via inhibition of Hsp90, a novel cellular target for the development of anti-CSC agents.
Conclusion
Ginseng-derived compounds that target cancer stem cells hold significant promise for treating a broad spectrum of cancers. Further research is essential to fully understand the intricate molecular mechanisms underlying the pharmacological activities of these compounds. This deeper understanding may pave the way for the development of more potent and targeted anti-cancer strategies, offering new hope in the ongoing battle against cancer.Reference
[1] Lee JS, Lee HY. Ginseng-derived compounds as potential anticancer agents targeting cancer stem cells [J]. J Ginseng Res. 2024;48(3):266-275. doi:10.1016/j.jgr.2024.03.003[2] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[3] Zhang WJ, Zhao KX, Zhang KY, et al. Advances in the biological characteristics and stem maintenance mechanisms of tumor stem cells[J]. Chin J Biotech, 2024, 40(2): 391-418.
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