Abstract
Glioblastoma (GBM), accounting for about 50 % of all gliomas, is the most common, malignant, and lethal primary brain tumor in adults. Up to now, there is no effective drug for GBM. 3‐O‐Acetyl‐11‐keto‐β‐boswellic acid (AKBA) is one of main active ingredients of the gum resin of Boswellia serrata and Boswellia carterri Birdw. AKBA was reported to inhibit the growth of many cancer cells; however, the precise molecular mechanisms of its anti‐cancer activities in GBM remain unclear. Here, we found that treatment of AKBA in U251 and U87‐MG glioma cells inhibited the cell proliferation, released the cellular LDH, decreased the DNA synthesis, and inhibited the migration, invasion, and colony formation of cells. AKBA also increased the apoptotic rate of cells, decreased the mitochondrial membrane potential, inhibited the activity of caspase 3/7, and decrased the protein expreesion of cleaved‐caspase 3, cleaved PARP in U251 and U87‐MG cells. RNA‐Sequencing analyses showed that AKBA suppressed the expression of pRB, FOXM1, Aurora A, PLK1, CCD25C, p‐CDK1, cyclin‐B1, Aurora B, and TOP2A while increased the expression of p21 and GADD45A, which was further validated by qRT‐PCR and Western blot analyses. These results demonstrated that AKBA induced mitochondrial dependent apoptosis in glioblastoma cells which was associated with arresting the cell cycle at G2/M phase by regulating the p21/ FOXM1/cyclin B1 pathway and inhibiting the mitosis of glioma cells by downregulating the Aurora B/ TOP2A pathway. Taken together, our findings suggest that AKBA might be a promising chemotherapy drug in the treatment of GBM.Support or Funding InformationNational Natural Science Foundation of China (N0. 81573454 for JINHUA WANG, N0. 81703536 for WAN LI and 81703565 for WEIQI FU), CAMS Innovation Fund for Medical Sciences (CIFMS)(2016‐I2M‐3‐007) and Natural Science Foundation of Beijing (7172142).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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