Curcuma Aeruginosa Roxb. [C. zedoaria non Rosc.] Inhibits Human Papillomavirus-related Cervical Cancer via Dipeptidyl Peptidase IV.

This study elucidated the effect and underlying mechanism of Curcuma aeruginosa Roxb. [C. zedoaria non Rosc.] (CAR) in human papillomavirus (HPV)-related cervical cancer treatment through a network pharmacology approach. Serum containing CAR was prepared using SD rats. The activities of CAR in HPV-related cervical cancer cell viability and migration/invasion were detected by using cell count kit and Transwell assays. Compounds in CAR and their targets were collected from TCMSP and SymMap. The cervical cancer-associated targets were searched from GeneCards and TTD databases. Genes targeted by HPV in human were collected from VISDB database. The networks were constructed using all the targets/compounds or HPV cervical cancer-related targets/compounds. The binding affinity of Furanodiene with Dipeptidyl peptidase IV (DPP4) was determined by the molecular docking method in CB-Dock2. Overexpression of DPP4 was used to discover the effects of dipeptidyl peptidase IV protein on anticancer activity of CAR. CAR-containing serum inhibited the cell viability and migration/invasion of SiHa and Ca Ski cells. Three CAR targets, DPP4, Nitric-oxide synthase, endothelial (NOS3), and Apoptosis regulator Bcl-2 (BCL2) were common with cervical cancer-related genes and HPV-targeted genes. NOS3 was targeted by Furanodiene, BCL2 was targeted by beta-elemene, and DPP4 was targeted by (-)-Epoxycaryophyllene, Zingiberene, Furanodiene, etc. Molecular docking of DPP4 with Furanodiene showed two positions with a Vina score of -6.8. Overexpression of DPP4 reversed the anticancer effects of CAR on HPV-related cervical cancer cells. CAR had inhibitory effects on HPV cervical cancer, possibly by downregulating the expression of DPP4.