Cytotoxic and Antiproliferative Effects of β-Mangostin on Rat C6 Glioma Cells Depend on Oxidative Stress Induction via PI3K/AKT/mTOR Pathway Inhibition

Abstract

Background

Glioma is the most common malignant tumor of the nervous system, which accounts for more than 45% of central nervous system tumors and seriously threatens our health. Because of high mortality rate, limitations, and many complications of traditional treatment methods, new treatment methods are urgently needed. β-Mangostin is a natural compound derived from the fruit of Garcinia mangostana L. and it has anticancer activity in several types of cancer cells. However, the antitumor effect of β-mangostin in glioma has not been clarified. Hence, this study aimed to investigate its therapeutic effects on gliomas.

Materials and Methods

To study the effect of β-mangostin on glioma cells, cell viability assay, reactive oxygen species production, cell cycle, apoptosis, and mitochondrial membrane potential were evaluated in the C6 cell line in vitro. Immunofluorescence and Western blotting were used to analyze protein expression and phosphorylation to study its mechanism of action. A subcutaneous xenograft model was used to investigate the effect of β-mangostin on tumorigenesis in vivo.

Results

We found that β-mangostin can inhibit glioma cell growth and induce oxidative damage in vitro. In addition, it reduces the phosphorylated form levels of PI3K, AKT and mTOR. Furthermore, the phosphorylated form levels of PI3K, AKT and mTOR were increased after the PI3K inhibitor was added. In vivo experiments showed that β-mangostin can inhibit tumor growth as shown by its reduced size and weight.

Conclusion

This study suggests that β-mangostin can inhibit cell proliferation and induce oxidative damage in cells. It is the first study to demonstrate that β-mangostin induces oxidative damage in glioma cells by inhibiting the PI3K/AKT/mTOR signaling pathway.

Keywords:

• glioma
• PI3K/AKT/mTOR
• oxidative damage
• Garcinia mangostana L.

Acknowledgments

We are deeply grateful to Professor Youmin Ying for his assistance in β-mangostin extraction.

Disclosure

Zhen Wang reports a patent licensed for Method for anticancer drug. The authors report no other potential conflicts of interest in this work.