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
3158 - Tobacco Retail Access and Tobacco Cessation Among Head and Neck Cancer (HNC) Survivors
Presenter: Lawson Eng
Session: Poster Display session 1
Resources:
Abstract
5511 - ASSERT: A Prospective, Observational Study Measuring Sodium Improvement and Outcomes in Patients Treated for Moderate to Severe Hyponatremia Secondary to Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) in Italy (Lung Cancer Cohort)
Presenter: Rossana Berardi
Session: Poster Display session 1
Resources:
Abstract
3821 - Efficacy and safety of controlled ovarian stimulation with or without letrozole co-administration for fertility preservation: A systematic review and meta-analysis.
Presenter: Benedetta Bonardi
Session: Poster Display session 1
Resources:
Abstract
2168 - Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy
Presenter: Tineke Vandenbroucke
Session: Poster Display session 1
Resources:
Abstract
5855 - Update of the registry of young women with cancer by the International Network of Cancer, Infertility and Pregnancy
Presenter: Charlotte Maggen
Session: Poster Display session 1
Resources:
Abstract
5156 - Erectile dysfunction in patients with metastatic renal cell carcinoma
Presenter: Ilya Tsimafeyeu
Session: Poster Display session 1
Resources:
Abstract
4992 - Exercise level, interest and preferences in cancer patients.
Presenter: Alice Avancini
Session: Poster Display session 1
Resources:
Abstract
3427 - Filling the Gaps in Informed Consent for Advanced Cancer Patients considering Phase 1 Oncology Trials - an in-depth Qualitative Study of Key Stakeholders at a large United Kingdom Phase 1 unit
Presenter: Abhijit Pal
Session: Poster Display session 1
Resources:
Abstract
3537 - Breast Cancer Patients’ Quality of Life: Real World Data
Presenter: Thanos Kosmidis
Session: Poster Display session 1
Resources:
Abstract
4761 - High-sensitivity troponin as a cardiotoxicity biomarker in breast cancer treatment
Presenter: Joana Simões
Session: Poster Display session 1
Resources:
Abstract