Induction of Apoptosis and Inhibition of Epithelial Mesenchymal Transition by α‐Mangostin in MG‐63 Cell Lines

Abstract

Osteosarcoma is the most common bone primary malignant tumor and nearly 30% of patients still die from osteosarcoma due to metastasis or recurrence. Thus, it is necessary to develop effective new chemotherapeutic agents for osteosarcoma treatment. α-Mangostin is a xanthone derivative shown to have antioxidant and anticarcinogen properties. However, the molecular mechanisms underlying the antimetastatic effects of osteosarcoma remain unclear. In metastasis progression, epithelial mesenchymal transition (EMT) is a process that plays important roles in development, cell polarity, and increased invasion and migration. This study focused on the induction of apoptosis and inhibition of EMT process by α-mangostin in human osteosarcoma cell line MG63. α-Mangostin treatments on MG63 cells not only showed the several lines of evidence of apoptotic cell death but also inhibited cell migration, invasion, and EMT-inducing transcription factor. In conclusion, we demonstrate that the α-mangostin induces apoptosis via mitochondrial pathway and suppresses metastasis of osteosarcoma cells by inhibiting EMT.

Ethanolic extract of mangosteen (Garcinia mangostana) pericarp as sensitivity enhancer of doxorubicin on MCF-7 cells by inhibiting P-glycoprotein

“…The growth inhibition by this extract could also be caused by the content of active substance namely α-mangostin. α-mangostin which is the major component of EEMP is capable to induce the cell death in oral squamous cell carcinoma cell (Kwak et al 2016) and to induce the apoptosis in human osteosarcoma cell line MG63 (Park et al 2018). α-mangostin has been shown to inhibit the proliferation pathway through p38 mitogen-activated protein kinase (MAPK) and to induce the apoptosis mechanism by increasing the levels of Bax, followed by the activation of the caspase 3 and caspase 9 (Lee et al 2016).…”

The Effect of Alpha Mangostin on Epithelial-Mesenchymal Transition on Human Hepatocellular Carcinoma HepG2 Cells Surviving Sorafenib via TGF-β/Smad Pathways

“… 16 We assume that the differences in the findings from this study with Xu et al and Park et al were most likely due to the difference in cell types. 15 , 16 The fact that their research was done in naïve cells were the main thing that contributes to this distinction. The difference between naïve cells and resistant cells was explained by Chen et al, who found a different downstream of the MAPK signaling pathway in untreated versus sorafenib-treated HCC cell lines.…”

“…Both studies showed that alpha mangostin suppressed EMT.Xu et al reported that alpha mangostin treatment in BxPc-3 and Panc-1 cells resulted in the reduction of EMT markers by inhibiting PI3K/Akt pathways, 15 whereas Park et al showed that alpha mangostin inhibit MAPK Pathways (ERK 1/2, JNK, and p38). 16 However, Park et al also showed that although E-cadherin expressions were increased, Snail protein expression in the dose of 10 µM was elevated significantly. 16 We assume that the differences in the findings from this study with Xu et al and Park et al were most likely due to the difference in cell types.…”

“…16 However, Park et al also showed that although E-cadherin expressions were increased, Snail protein expression in the dose of 10 µM was elevated significantly. 16 We assume that the differences in the findings from this study with Xu et al and Park et al were most likely due to the difference in cell types. 15,16 The fact that their research was done in naïve cells were the main thing that contributes to this distinction.…”

“…Reports in pancreatic cancer and bone osteosarcoma indicate that alpha mangostin was able to suppress EMT. 15 , 16 Studies on alpha mangostin in HepG2 cells have been done before by Wudtiwai et al and Mohamed et al 17 , 18 However, none have investigated the effect of alpha mangostin in EMT through TGF-β/Smad pathways in the sorafenib-surviving liver carcinoma model. Thus, the exact molecular mechanism of alpha mangostin is still poorly understood.…”