CONTEXT

Sanguinarine (SAG) is the most abundant constituent of (Willd.) R. Br. (Popaceae). SAG has shown antimammary and colorectal metastatic effects in mice , suggesting its potential for cancer chemotherapy.

OBJECTIVE

To determine the antimetastatic effect and underlying molecular mechanisms of SAG on melanoma.

MATERIALS AND METHODS

CCK8 assay was used to determine the inhibition of SAG on the proliferation of A375 and A2058 cells. Network pharmacology analysis was applied to construct a compound-target network and select potential therapeutic targets of SAG against melanoma. Molecular docking simulation was conducted for further analysis of the selected targets. migration/invasion/western blot assay with 1, 1.5, 2 μM SAG and effect of 2, 4, 8 mg/kg SAG in xenotransplantation model in nude mice.

RESULTS

The key targets of SAG treatment for melanoma were mainly enriched in PI3K-AKT pathway, and the binding energy of SAG to PI3K, AKT, and mTOR were -6.33, -6.31, and -6.07 kcal/mol, respectively. SAG treatment inhibited the proliferation, migration, and invasion ability of A375 and A2058 cells ( < 0.05) with IC values of 2.378 μM and 2.719 μM, respectively. It also decreased the phosphorylation levels of FAK, PI3K, AKT, mTOR and protein expression levels of MMP2 and ICAM-2. In the nude mouse xenograft model, 2, 4, 8 mg/kg SAG was shown to be effective in inhibiting tumour growth.

CONCLUSIONS

Our research offered a theoretical foundation for the clinical antitumor properties of SAG, further suggesting its potential application in the clinic.