α-Mangostin suppresses 12-o-tetradecanoylphorbol-13- acetate-mediated matrix metalloproteinase-9 expression in human osteosarcoma cells U2OS

Purpose: To investigate the effect of α-mangostin on matrix metalloproteinase (MMP)-2 and MMP-9 expression in U2OS human osteosarcoma cell lines.
Methods: Cytotoxicity of α-mangostin on U2OS cells was determined by MTT assay. MMP-2 and MMP-9 activities, and mRNA expression of α-mangostin-treated U2OS cells were evaluated using gelatin zymography and real-time polymerase chain reaction (PCR), respectively. Wound healing assay was used to determine whether α-mangostin inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced migration of U2OS cells.
Results: U2OS viability was significantly decreased when cells were exposed to α-mangostin at 2.5 and 5 μg/mL compared to the untreated control (p < 0.05). α-Mangostin inhibited MMP-2 and MMP-9 activities stimulated by TPA at concentrations of 1.0, 1.5, and 2.0 μg/mL. MMP-9 mRNA expression of TPA treated U2OS was down-regulated by α-mangostin. However, MMP-2 mRNA levels remained unchanged. Would healing assay revealed that α-mangostin (2 μg/mL) significantly inhibited TPA-induced U2OS migration compared to the control (p < 0.05).
Conclusion: This is the first study reporting the inhibitory effects of α-mangostin on TPA-mediated MMP-9 expression and TPA-induced migration of U2OS cells. Thus, it is a potential therapeutic agent for the treatment of osteosarcoma.

Keywords
α-Mangostin; Matrix metalloproteinase; Osteosarcoma; Cell migration; 12-OTetradecanoylphorbol-13-acetate; Wound healing; Zymography