Original articles
Wan Li, Liwen Ren, Xiangjin Zheng, Jinyi Liu, Jinhua Wang, Tengfei Ji, Guanhua Du. 3-O-Acetyl-11-keto-β-boswellic acid ameliorated aberrant metabolic landscape and inhibited autophagy in glioblastoma[J]. Acta Pharmaceutica Sinica B, 2020, 10(2): 301-312

3-O-Acetyl-11-keto-β-boswellic acid ameliorated aberrant metabolic landscape and inhibited autophagy in glioblastoma
Wan Lia,b, Liwen Rena,b, Xiangjin Zhenga,b, Jinyi Liua,b, Jinhua Wanga,b, Tengfei Jib, Guanhua Dua,b
a The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China;
b Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
Glioblastoma is the most common and aggressive primary tumor in the central nervous system, accounting for 12%-15% of all brain tumors. 3-O-Acetyl-11-keto-β-boswellic acid (AKBA), one of the most active ingredients of gum resin from Boswellia carteri Birdw., was reported to inhibit the growth of glioblastoma cells and subcutaneous glioblastoma. However, whether AKBA has antitumor effects on orthotopic glioblastoma and the underlying mechanisms are still unclear. An orthotopic mouse model was used to evaluate the anti-glioblastoma effects of AKBA. The effects of AKBA on tumor growth were evaluated using MRI. The effects on the alteration of metabolic landscape were detected by MALDIMSI. The underlying mechanisms of autophagy reducing by AKBA treatment were determined by immunoblotting and immunofluorescence, respectively. Transmission electron microscope was used to check morphology of cells treated by AKBA. Our results showed that AKBA (100 mg/kg) significantly inhibited the growth of orthotopic U87-MG gliomas. Results from MALDI-MSI showed that AKBA improved the metabolic profile of mice with glioblastoma, while immunoblot assays revealed that AKBA suppressed the expression of ATG5, p62, LC3B, p-ERK/ERK, and P53, and increased the ratio of p-mTOR/mTOR. Taken together, these results suggested that the antitumor effects of AKBA were related to the normalization of aberrant metabolism in the glioblastoma and the inhibition of autophagy. AKBA could be a promising chemotherapy drug for glioblastoma.
Key words:    Glioblastoma    AKBA    MALDI-MSI    Phospholipids    Autophagy   
Received: 2019-09-27     Revised: 2019-11-02
DOI: 10.1016/j.apsb.2019.12.012
Funds: This work was supported by National Natural Science Foundation of China (No. 81573454 for Jinhua Wang and No. 81703536 for Wan Li) and supported by Beijing Natural Science Foundation (7172142,China). This work was also supported by CAMS Innovation Fund for Medical Sciences (2016-I2M-3-007, China) and Science and Technology Major Projects for "Major New Drugs Innovation and Development" (2018ZX09711001-005-025, China).
Corresponding author: Jinhua Wang, Tengfei Ji, Guanhua Du     Email:wjh@imm.ac.cn;jitf@imm.ac.cn;dugh@imm.ac.cn
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Wan Li
Liwen Ren
Xiangjin Zheng
Jinyi Liu
Jinhua Wang
Tengfei Ji
Guanhua Du

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