Abstract
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 TPAinduced 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
Highlights
Osteosarcoma is the most common primary bone malignancy found in children and young adults
Cytotoxicity of α-mangostin was first determined by treating U2OS cells with various concentrations of α-mangostin (0, 0.5, 1.0, 1.5, 2.0, 2.5 and 5 μg/mL) for 24 and 48 h followed by MTT assay
Compared to the non-TPA treated cells, TPA significantly increased the matrix metalloproteinase (MMP)-9 activity. This effect was not observed for MMP-2. α-Mangostin significantly inhibited MMP-2 and MMP-9 activities stimulated by TPA at concentrations of 1.0, 1.5, and 2.0 μg/mL. (Fig 2)
Summary
Osteosarcoma is the most common primary bone malignancy found in children and young adults. It usually occurs in the distal long bones, but can affect other bones in the body [1]. A number of chemotherapeutic agents have been used to treat osteosarcoma, survival rate of patients has not been substantially improved [2]. One of the primary reasons for the failure of current treatments is that patients with stage IV cancer often develop resistance to anticancer agents [3]. Gelatinases (MMP-2 and MMP-9) are members of MMP family that plays an important role in the progression and metastasis of human cancers [4]. A recent study demonstrated that MMP-2 overexpression was related to a poor prognosis [6] and high MMP-9 expression were significantly associated with lower overall survival compared to their counterparts with low or undetectable MMP-9 expression [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
