Abstract 3154
Background
The development of a novel therapy for malignant glioma is a vigorous area in both chemistry and cancer research. Previously, we reported that the small molecule naphtho [2, 3-f] quinoxaline-7, 12-dione (CC12) effectively inhibits the proliferation of several cancers. In this study, we further investigated the therapeutic effects of CC12 on human glioblastoma (GBM) cells and clarified underlying mechanisms of these effects.
Methods
Human GBM cell lines, U118MG and U87MG, were used for in vitro and in vivo. Analysis of CC12 effects on cell cycle and apoptosis, while nude mice bearing xenograft of the tumor cells were used for in-vivo analysis of CC12 effects on tumor metabolism and size by using animal positron emission tomography (PET). DNA fragmentation, mitochondrial membrane potential change, cell cycle inhibiion and apoptosis were labelled with fluorescent tracers or antibodies, and followed by measured with flow cytometry. Apoptotic-associated proteins were quantified by immunoblot analysis. Tumors in animals were labelled with [18F]-fluorodeoxyglucose ([18F]-FDG), and imaged by animal-PET. Tumor tissue was collected and weighed, and vital organs including the heart, kidneys and liver were extracted for hematoxylin and eosin staining.
Results
We found that CC12 induced cell cycle arrest as GBM cells were accumulated in the subG1 and G2/M phases in a dose- and time-dependent manner. This effect was caused by DNA damage response in GBM cells. Moreover, the treatment of CC12 reduced the expression of decoy receptor 3 and disrupted the mitochondrial membrane signaling cascade in GBM cells, leading to apoptosis of the cells. In the heterotopic mice model, we found that the size of the GBM cell xenografts was decreased following the treatment of CC12, indicated by [18F]-FDG coupled with PET.
Conclusions
These findings provide evidence from molecular, cellular, and physiological levels that strongly suggest that CC12 is a promising small-molecule agent for human GBM.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.
Resources from the same session
2185 - Sequential treatment with afatinib followed by 3rd generation EGFR-TKI – subgroup analysis of the GIDEON trial: a prospective non-interventional study (NIS) in EGFR mutated NSCLC patients in Germany
Presenter: Wolfgang Brückl
Session: Poster Display session 1
Resources:
Abstract
1524 - Effectiveness of sequencing TKIs in patients with EGFR mutation-positive Non-small-Cell Lung Cancer (NSCLC): A French National medico administrative claim database analysis
Presenter: Nicolas Girard
Session: Poster Display session 1
Resources:
Abstract
5733 - Phase II study of osimertinib in NSCLC patients with EGFR exon 20 insertion mutation: A multicenter trial of the Korean Cancer Study Group (LU17-19)
Presenter: Tae Min Kim
Session: Poster Display session 1
Resources:
Abstract
5440 - Different stories for different EGFR exon 19 deletion variants
Presenter: Chao Zhao
Session: Poster Display session 1
Resources:
Abstract
2982 - Safety and activity of alflutinib in patients with advanced EGFR T790M mutation non-small cell lung cancer who progressed after EGFR-TKI therapy
Presenter: Yuan-Kai Shi
Session: Poster Display session 1
Resources:
Abstract
4002 - Afatinib followed by osimertinib in patients with EGFR mutation-positive (EGFRm+) advanced NSCLC: updated data from the GioTag real-world study
Presenter: Maximilian Hochmair
Session: Poster Display session 1
Resources:
Abstract
2941 - Treatment patterns of EGFR mt+ NSCLC IV pts: Real world data of the NOWEL network
Presenter: Julia Roeper
Session: Poster Display session 1
Resources:
Abstract
4154 - TP53 mutations predicts worse prognosis in EGFR-mutated NSCLC patients receiving TKIs in first- or further line of treatment
Presenter: Matteo Canale
Session: Poster Display session 1
Resources:
Abstract
1175 - HER3 ligand heregulin expression and clinical implication in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer treated with EGFR-tyrosine kinase inhibitors
Presenter: Kimio Yonesaka
Session: Poster Display session 1
Resources:
Abstract
2023 - Patients with brain metastases treated with afatinib in clinical practice – results from the prospective non-interventional study GIDEON
Presenter: Eckart Laack
Session: Poster Display session 1
Resources:
Abstract