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
5344 - Global trends in population-based survival for 303,169 adults diagnosed with glioblastoma in 44 countries during 2000-2014 (CONCORD-3)
Presenter: Fabio Girardi
Session: Poster Display session 1
Resources:
Abstract
3088 - Spanish Survey of treatment recommendations for elderley patients with glioblastoma
Presenter: María Ángeles Vaz Salgado
Session: Poster Display session 1
Resources:
Abstract
3484 - Updated analysis of the National Registry of Nervous System Tumors in Spain (RETSINE). RETSINE: National Registry of Nervous System Tumors of the Spanish Research Group in Neuro-oncology (GEINO) and Spanish Infrequent and Orphan Tumors Group (GETHI)
Presenter: Isaac Ceballos Lenza
Session: Poster Display session 1
Resources:
Abstract
4737 - Development and validation of novel nomograms predicting survival of malignant ependymoma patients: A population-based study
Presenter: Alzhraa Abbas
Session: Poster Display session 1
Resources:
Abstract
4740 - Characteristics, incidence, and survival of primary cerebral lymphoma: A population based study
Presenter: Sherief Ghozy
Session: Poster Display session 1
Resources:
Abstract
5362 - Trends in Incidence and Survival Analyses of Adult-onset Medulloblastoma
Presenter: Feifei Lin
Session: Poster Display session 1
Resources:
Abstract
3868 - Meta of classical chemotherapy compared with high-dose chemotherapy combined with autologous stem cell transplantation in newly diagnosed medulloblastoma patients after radiotherapy
Presenter: Mengting Zhang
Session: Poster Display session 1
Resources:
Abstract
4446 - Effect of cumulative dose of maintenance temozolomide on overall survival in patients with high grade glia tumors: a single institution analysis
Presenter: Marta Nerone
Session: Poster Display session 1
Resources:
Abstract
5119 - Markers of systemic inflammation correlate with survival prognosis in patients with newly diagnosed brain metastases
Presenter: Angelika Starzer
Session: Poster Display session 1
Resources:
Abstract
3882 - Venous Thromboembolism and Intracranial Hemorrhage in Patients with High-grade Glioma
Presenter: Clara Borges
Session: Poster Display session 1
Resources:
Abstract