Drug Design, Development and Therapy (Dec 2020)

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

  • Li K,
  • Wu L,
  • Chen Y,
  • Li Y,
  • Wang Q,
  • Li M,
  • Hao K,
  • Zhang W,
  • Jiang S,
  • Wang Z

Journal volume & issue
Vol. Volume 14
pp. 5315 – 5324

Abstract

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Kaiqiang Li,1– 3,* Lingling Wu,1,* Yili Chen,4,* Yuanyuan Li,5 Qianni Wang,1 Min Li,3 Ke Hao,2,3 Wei Zhang,3 Shanshan Jiang,2 Zhen Wang1,2 1School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325027, People’s Republic of China; 2Research Center of Blood Transfusion Medicine, Ministry of Education Key Laboratory of Laboratory Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, People’s Republic of China; 3Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, People’s Republic of China; 4College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, People’s Republic of China; 5School of Pharmacy, Hangzhou Medical College, Hangzhou 310014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shanshan Jiang; Zhen WangZhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, People’s Republic of ChinaTel +86 571-87666666Fax +86 571-85131448Email [email protected]; [email protected]: 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.

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