Context
Sanguinarine (SAG) is the most abundant constituent of
Macleaya cordata
(Willd.) R. Br. (Popaceae). SAG has shown antimammary and colorectal metastatic effects in mice
in vivo
, 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.
In vitro
migration/invasion/western blot assay with 1, 1.5, 2 μM SAG and
in vivo
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 (
p
< 0.05) with IC
50
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.