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3-O-Acetyl-11-keto- β -boswellic acid ameliorated aberrant metabolic landscape and inhibited autophagy in glioblastoma.
Acta Pharmaceutica Sinica B ( IF 14.5 ) Pub Date : 2020-01-10 , DOI: 10.1016/j.apsb.2019.12.012
Wan Li 1, 2 , Liwen Ren 1, 2 , Xiangjin Zheng 1, 2 , Jinyi Liu 1, 2 , Jinhua Wang 1, 2 , Tengfei Ji 2 , Guanhua Du 1, 2
Affiliation  

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 MALDI-MSI. 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.

中文翻译:

3-O-乙酰基-11-酮-β-乳香酸可改善胶质母细胞瘤的异常代谢状况并抑制自噬。

胶质母细胞瘤是中枢神经系统中最常见和侵袭性的原发性肿瘤,占所有脑瘤的12%-15%。据报道,3-O-乙酰基-11-酮-β-乳香酸(AKBA)是乳香中最有效的树胶树脂成分之一,可抑制胶质母细胞瘤细胞和皮下胶质母细胞瘤的生长。但是,AKBA是否对原位胶质母细胞瘤具有抗肿瘤作用及其潜在机制尚不清楚。使用原位小鼠模型评估AKBA的抗成胶质细胞瘤作用。使用MRI评估AKBA对肿瘤生长的影响。通过MALDI-MSI检测对代谢状况改变的影响。分别通过免疫印迹和免疫荧光确定了通过AKBA处理减少自噬的潜在机制。用透射电子显微镜检查经AKBA处理的细胞的形态。我们的结果表明,AKBA(100 mg / kg)显着抑制原位U87-MG神经胶质瘤的生长。MALDI-MSI的结果表明AKBA改善了胶质母细胞瘤小鼠的代谢状况,而免疫印迹分析表明AKBA抑制了ATG5,p62,LC3B,p-ERK / ERK和P53的表达,并增加了p-mTOR的比例/ mTOR。综上所述,这些结果表明AKBA的抗肿瘤作用与胶质母细胞瘤中异常代谢的正常化和自噬的抑制有关。AKBA可能是胶质母细胞瘤的有前途的化疗药物。MALDI-MSI的结果表明AKBA改善了胶质母细胞瘤小鼠的代谢状况,而免疫印迹分析表明AKBA抑制了ATG5,p62,LC3B,p-ERK / ERK和P53的表达,并增加了p-mTOR的比例/ mTOR。综上所述,这些结果表明AKBA的抗肿瘤作用与胶质母细胞瘤中异常代谢的正常化和自噬的抑制有关。AKBA可能是胶质母细胞瘤的有前途的化疗药物。MALDI-MSI的结果表明AKBA改善了胶质母细胞瘤小鼠的代谢状况,而免疫印迹分析表明AKBA抑制了ATG5,p62,LC3B,p-ERK / ERK和P53的表达,并增加了p-mTOR的比例/ mTOR。综上所述,这些结果表明AKBA的抗肿瘤作用与胶质母细胞瘤中异常代谢的正常化和自噬的抑制有关。AKBA可能是胶质母细胞瘤的有前途的化疗药物。这些结果表明AKBA的抗肿瘤作用与胶质母细胞瘤中异常代谢的正常化和自噬的抑制有关。AKBA可能是胶质母细胞瘤的有前途的化疗药物。这些结果表明AKBA的抗肿瘤作用与胶质母细胞瘤中异常代谢的正常化和自噬的抑制有关。AKBA可能是胶质母细胞瘤的有前途的化疗药物。
更新日期:2020-01-10
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