different modes of mechanism of gamma-mangostin and alpha-mangostin to inhibit cell migration of triple-negative breast cancer cells concerning cxcr4 downregulation and ros generation

Background: two mangostin compounds, gamma-mangostin and alpha-mangostin, show anticancer properties through the inhibition of cell proliferation and cell migration. metastatic triple-negative breast cancer (tnbc) cells, including mda-mb-231, highly express c-x-c chemokine receptor type 4 (cxcr4) to maintain reactive oxygen species (ros) and cell migration. objectives: this study was performed to analyze and compare different modes of action of γ-mangostin and α-mangostin as antimigratory effects targeted on cxcr4in mda-mb-231 as a model of tnbc cell. methods: this study investigated the effect of γ-mangostin and α-mangostin using a series of assays, including cell counting kit-8 (cck-8) assay for cytotoxicity, wound healing assay for migration study, quantitative real-time polymerase chain reaction (qrt-pcr) for gene expression analysis, and flow cytometry for ros measurement, along with in silico study to observe the binding between the compound and cxcr4. results: the findings revealed half maximal inhibitory concentration (ic50) values of 25 and 20 μm for γ-mangostin and α-mangostin in mda-mb 231 cells, respectively. moreover, a concentration of 10 μm was used for the migration assay. both γ-mangostin and α-mangostin significantly suppressed cell migration within 24 hours. the present gene expression studies revealed the downregulation of key migration-associated genes, namely farp, cxcr4, and lphn2, upon γ-mangostin treatment but not α-mangostin. additionally, both γ-mangostin and α-mangostin increased cellular ros generation, highlighting the same effect of γ-mangostin and α-mangostin ros elevation to inhibit cancer cell migration. molecular docking simulations further suggested a potential interaction between γ-mangostin and α-mangostin with cxcr4in high affinity. conclusions: these findings suggest that both γ-mangostin and α-mangostin inhibit breast cancer cell migration and induce cellular ros levels in mda-mb-231 cells; notably, γ-mangostin suppresses its activity to inhibit mda-mb-231 cell migration.