Therapeutic mechanism of aqueous extract of Semiliquidambar cathayensis Chang root for pancreatic cancer: the active components, therapeutic targets and pathways

doi:10.12122/j.issn.1673-4254.2024.07.13

Abstract

Abstract:

Objective To explore the key targets and signaling pathways in the therapeutic mechanism of Semiliquidambar cathayensis Chang (SC) root against pancreatic cancer network pharmacology and molecular docking studies and cell experiments. Methods The targets of SC and pancreatic cancer were predicted using the network pharmacological database, the protein-protein interaction network was constructed, and pathways, functional enrichment and molecular docking analyses were performed. CCK-8 assay was used to test the inhibitory effect of the aqueous extract of SC root on 8 cancer cell lines, and its effects on invasion, migration, proliferation, and apoptosis of pancreatic cancer cells were evaluated. Western blotting was performed to verify the results of network pharmacology analysis. Results We identified a total of 18 active components in SC, which regulated 21 potential key targets in pancreatic cancer. GO and KEGG pathway enrichment analyses showed that these targets were involved mainly in the biological processes including protein phosphorylation, signal transduction, and apoptosis and participated in cancer signaling and PI3K-Akt signaling pathways. Among the 8 cancer cell lines, The aqueous extract of SC root produced the most obvious inhibitory effect in pancreatic cancer cells, and significantly inhibited the invasion, migration, and proliferation and promoted apoptosis of pancreatic cancer Panc-1 cells (P<0.05). Western blotting confirmed that SC significantly inhibited the phosphorylation levels of PI3K and AKT in Panc-1 cells (P<0.001). Conclusion The therapeutic effect of SC root against pancreatic cancer effects is mediated by its multiple components that act on different targets and pathways including the PI3K-Akt pathway.

Key words: Semiliquidambar cathayensis Chang, pancreatic cancer, network pharmacology, molecular docking, pathway analysis

Yan HUANG, Lulu QIN, Shaoxing GUAN, Yanping GUANG, Yuru WEI, Ailing CAO, Dongmei LI, Guining WEI, Qibiao SU. Therapeutic mechanism of aqueous extract of Semiliquidambar cathayensis Chang root for pancreatic cancer: the active components, therapeutic targets and pathways[J]. Journal of Southern Medical University, 2024, 44(7): 1336-1344.

Figures/Tables 8

Fig.1 IC50 of Semiliquidambar cathayensis Chang root extract (SC) and 5-fluorouracil for different cancer cell lines. A-H: IC50 of Semiliquidambar cathayensis Chang against T98G, MCF-7, HePG2, Panc-1, A549, HCT116, A375, and NCI-H1299 cells; I: IC50 of 5-FU against Panc-1 cells.

Tab.1 Main active components in Semiliquidambar cathayensis Chang root

Ingredient	CAS	Degree
Quercetin	117-39-5	52
Kaempferol	520-18-3	51
Naringenin	480-41-1	50
2,3,8-Tri-O-methylellagic acid	1617-49-8	31
Oleanolic acid	508-02-1	29
Paeoniflorin	23180-57-6	27
Bergaptol	486-60-2	26
Palmitic acid	57-10-3	25
Fraxin	524-30-1	20
Beta-Sitosterol	83-46-5	17
Songorine	509-24-0	16
Atractylenolide-1	73069-13-3	14
Daucosterol	474-58-8	14
Hyperoside	482-36-0	11
Gallic acid	149-91-7	10
Isoquercitrin	21637-25-2	9
Rutin	153-18-4	9
Acteoside(Verbascoside)	61276-17-3	5

Fig.2 Venn diagram of the targets of Semiliquidambar cathayensis Chang and pancreatic cancer.

Fig.3 Prediction of the key components of Semiliquidambar cathayensis Chang. The circles indicate the target points of the intersection targets, and the V-shaped marks are the chemical components of Semiliquidambar cathayensis Chang. A darker color indicates a larger degree value.

Fig.4 Prediction of the key targets of Semiliquidambar cathayensis Chang and pancreatic cancer. The V-shaped marks indicate the key targets of Semiliquidambar cathayensis Chang, and the circles are other target points. A darker color indicates a larger degree value.

Fig.5 GO analysis of the therapeutic mechanism of Semiliquidambar cathasis Chang against pancreatic cancer.

Fig.6 KEGG analysis of the therapeutic mechanism of Semiliquidambar cathasis Chang against pancreatic cancer.

Tab.2 Molecular docking score of the key components against the key targets

Affinity	Naringenin	2, 3, 8-Tri-O-methylellagic acid	Quercetin	Kaempferol	Oleanolic acid
HSP90AA1	-8.9	-9.3	-9.3	-9.4	-7.0
SRC	-8.3	-7.9	-8.8	-8.6	-9.1
STAT3	-7.7	-7.2	-8.1	-7.8	-6.9
PIK3R1	-8.3	-6.1	-8.6	-8.7	-9.7
AKTI	-8.7	-8.5	-7.9	-7.9	-8.1

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