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

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. ß-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 ß-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 ß-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 ß-mangostin on tumorigenesis in vivo. RESULTS: We found that ß-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 ß-mangostin can inhibit tumor growth as shown by its reduced size and weight. CONCLUSION: This study suggests that ß-mangostin can inhibit cell proliferation and induce oxidative damage in cells. It is the first study to demonstrate that ß-mangostin induces oxidative damage in glioma cells by inhibiting the PI3K/AKT/mTOR signaling pathway.

C21 Fraction Refined from Marsdenia tenacissima-Induced Apoptosis is Enhanced by Suppression of Autophagy in Human Gastric Cell Lines.

C21 steroidal glycosides have been extensively reported for treating several types of cancer and are widely found in Marsdenia tenacissima. In this study, a C21 fraction was synthesized from M. tenacissima, and its anti-cancer potency was assessed against in vitro gastric cell lines BGC-823, SGC-7901, and AGS. Significant growth inhibition and cell cycle arrest were observed in C21 fraction-treated gastric cancer cells. The results of apoptotic staining techniques in C21 fraction-treated gastric cells were confirmed with excess reactive oxygen species generation. Moreover, SOD and H2O2 levels were increased by C21 fraction, especially when combined with chloroquine (CQ). The apoptotic inducing potential of C21 fraction was also evidenced by upregulation of proapoptotic proteins cleaved-PARP and BAX and downregulation of antiapoptotic proteins Bcl-2 and p-AKT by western blot, especially in the presence of the autophagy inhibitor CQ. The results showed that the apoptosis of gastric cancer cells caused by C21 fraction was enhanced by inhibiting autophagy. The current findings reveal a new mechanism for the antitumor activity of C21 fraction on gastric cancer.