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

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 βmangostin 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.

Cpne3 Regulates the Cell Proliferation and Apoptosis in Human Gbm via the Activation of Pi3k/akt Signaling Pathway

“…Previous studies have demonstrated that the PI3K/AKT pathway played a key role in modulating cell proliferation and apoptosis [14,15]. In glioma studies, multiple evidences revealed that the activation of PI3K/AKT pathway could enhance cell proliferation in a mTOR dependent or independent way [16][17][18]. However, as far as we could reach, no convincing evidence showed the regulatory effect of CPNE3 on PI3K/AKT pathway.…”

CPNE3 regulates the cell proliferation and apoptosis in human Glioblastoma via the activation of PI3K/AKT signaling pathway

“…Previous studies have demonstrated that the PI3K/AKT pathway played a key role in modulating cell proliferation and apoptosis [14,15]. In glioma studies, multiple evidences revealed that the activation of PI3K/AKT pathway could enhance cell proliferation in a mTOR dependent or independent way [16][17][18]. In primary breast tumors, high CPNE3 RNA levers significantly correlate with ERBB2 amplification [10].…”

Platelet-Tumor Cell Hybrid Membrane-Camouflaged Nanoparticles for Enhancing Therapy Efficacy in Glioma

“… 46 Our previous studies have shown that the apoptosis of glioma cells by β-mangostin treatment is accompanied by BAX mitochondrial distribution, oligomerization, and caspase 3 activation. 31 Physical and chemical properties of β-mangostin can be effectively improved by encapsulation into NPs. CCK8 assay showed that β-PCNPs significantly inhibited the proliferation of C6 glioma cells as compared with that by both bare core NPs and single cell membrane-coated NPs.…”

“…30 Our previous study showed that β-mangostin, the major component of Garcinia mangostana L. extract, has excellent anti-proliferative effects in C6 glioma cells, which result from oxidative damage-induced cell death through PI3K/AKT/mTOR pathway inhibition. 31 However, aqueous solubility, tumor selectivity or targeting, and BBB penetration rate of β-mangostin does not meet clinical requirements.…”