Professor Kim Yinghua's research team has made new progress in the field of ginsenoside targeted tumor inhibition

Professor Jin Yinghua's research team and the first report of the human target of ginsenoside Rh2 in 2017, a series of new progress have been made: 1) HSP90 protein is a cancer marker protein
that is highly expressed in various cancers such as liver cancer, bladder cancer, esophageal cancer and lung cancer and is positively associated with the poor prognosis of patients.
As a molecular chaperone, it mediates the folding and stabilization of a large number of mutant proteins in cancer cells, thereby helping the survival, growth and metastasis
of cancer cells.
Professor Jin Yinghua's research team was surprised to find that Hsp90A is a potential target protein of ginsenoside Rh2 in the early stage of human target screening using phage display technology, and it was proved that ginsenoside Rh2 can simultaneously bind to ATP in the Hsp90A amino segment through molecular docking calculation and protein thermal drift analysis The binding site and MC segment CDC37 binding domain effectively inhibited the chaperone activity
of Hsp90A.
It was further demonstrated that the targeted inhibition of Hsp90A by ginsenoside Rh2 triggered the proteasomal degradation of the key regulatory kinases CDK4/CDK6, CDK1 and CDK2 in the cell cycle, thereby inhibiting phosphorylation of Rb protein and cell cycle G0/G1 Period block.

As we all know, the mutation of Rb pathway is a necessary condition for cell carcinogenesis, so the effective inhibition of Rb pathway by ginsenosides is not only beneficial to the treatment of cancer with high expression of Hsp90A such as liver cancer, bladder cancer, esophageal cancer and lung cancer, but also suggests its universal prevention and treatment effect on tumors (first author Chen Chen, J.
Mol.
Sci.
）； 2) Elucidating that ginsenosides Rg5 and Rk1 inhibit the transcriptional activity of NF-k appa B by targeting annexin A2, thereby inhibiting drug resistance in tumor cells (first author Yushi Wang, Protein Cell）； 3) It was demonstrated that ginsenoside G-Rh2 inhibits the proangiogenic effect of tumor cells by targeting the Annexin A2-STAT3-VEGF pathway (first author Yushi Wang, J.
Mol.
Sci ）； 4) Inhibit the metastasis of tumor cells by targeting the Annexin A2-NF-kappa B pathway (first author Yushi Wang, Biomolecules).

NF- kappa B and STAT3 are transcription factors that play a key role in the formation and maintenance of tumor microenvironment, and the inhibitory effect of rare ginsenosides on these transcription factors strongly suggests that as natural compounds, ginsenosides can effectively prevent tumor occurrence, development and metastasis by targeting a variety of key tumor regulatory proteins and signal transduction pathways
。 The above research was supported by the Jilin Provincial Science and Technology Department and the Jilin Provincial School Co-construction Plan Special Project.

Ginseng is a precious plant with the reputation of "the king of 100 herbs and the first of 100 medicines", and has been used in
China for 4,000 years.
Professor Jin Yinghua's team is using modern biological means to analyze the precious clinical experience condensed by Chinese civilization in the process of thousands of years of ginseng application, promote ginseng to the world, and provide material basis and theoretical guidance
for overcoming difficult human diseases.

References

1Chen Chen, Yu-Shi Wang, En-Ting Zhang, Gang-Ao Li, Wen-Yuan Liu, Yang Li, and Ying-Hua Jin * (20S) Ginsenoside Rh2 exerts its anti‐tumor effect by disrupting the HSP90A‐Cdc37 system in human liver cancer cells,Int.
J.
Mol.
Sci.
2021, 22, 13170.

The full text of the paper is linked

2Yu-Shi Wang,He Li,Hongyan Zhu, Yang Li,Ying-Hua Jin *Identification of natural compounds targeting Annexin A2 with an anti-cancer effect, Protein Cell,2018, 9(6):568–579

Full text of the paper link

3Yu-Shi Wang, Chen Chen, Shi-Yin Zhang, Yang Li and Ying-Hua Jin*(20S) Ginsenoside Rh2 Inhibits STAT3/VEGF Signaling by Targeting Annexin A2, Int.
J.
Mol.
Sci.
2021,22, 9289，doi: 10.
3390/ijms22179289.

Full text of the paper is linked

4Yu-Shi Wang,He Li,Yang Li,Shiyin Zhang, Ying-Hua Jin *(20S)G-Rh2 Inhibits NF-kB Regulated Epithelial-Mesenchymal Transition by Targeting Annexin A2, Biomolecules,2020, 31; 10(4): 528

Full text of the paper link https://pubmed.
ncbi.
nlm.
nih.
gov/32244350/

5 He Li, Chunxiao Han, Chen Chen, Guanghong Han*, and Yang Li* (20S) Ginsenoside Rh2-Activated, Distinct Apoptosis Pathways in Highly and Poorly Differentiated Human Esophageal Cancer Cells, Molecules，2022, 27, 5602

Full text of the paper is linked