Abstract
Glioblastoma Multiforme (GBM) is an aggressive form of brain Tumor that has few cures. In this study, we analyze the anti-proliferative effects of a new molecule JQ1 against GBMs induced in Wistar Rats. JQ1 is essentially a Myc inhibitor. c-Myc is also known for altering the biochemistry of a tumor cell. Therefore, the study is intended to analyze certain other oncogenes associated with c-Myc and also the change in cellular biochemistry upon c-Myc inhibition. The quantitative analysis of gene expression gave a co-expressive pattern for all the three genes involved namely; c-Myc, Bcl-2, and Akt. The cellular biochemistry analysis by transmission electron microscopy revealed high glycogen and lipid aggregation in Myc inhibited cells and excessive autophagy. The study demonstrates the role of c-Myc as a central metabolic regulator and Bcl-2 and Akt assisting in extending c-Myc half-life as well as in regulation of autophagy, so as to regulate cell survival on the whole. The study also demonstrates that transient treatment by JQ1 leads to aggressive development of tumor and therefore, accelerating death, emphasizing the importance of dosage fixation, and duration for clinical use in future.
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Abbreviations
- BET:
-
Bromodomain and extra terminal
- EGFR:
-
Epidermal growth factor receptor
- PKM2:
-
Pyruvate kinase muscle isozyme 2
- IDH:
-
Isocitrate dehydrogenase
- HIF:
-
Hypoxia-inducible factor
- ACL:
-
ATP citrate lyase
- ACC:
-
Acetyl-CoA carboxylase
- FASN:
-
Fatty acid synthase
- GSK:
-
Glycogen synthase kinase
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Acknowledgments
The study was supported by University Grants Commission, New Delhi, India. We thank the Sophisticated Analytical Instrument Facility (SAIF)-Department of Anatomy, AIIMS, New Delhi, India for providing microscopes in Electron Microscopy. We thank Dr. Aparna Rajagopalan for her critical reading and editing. We also thank University of Madras for all the infrastructure support in carrying out the experiments.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Rajagopalan, V., Vaidyanathan, M., Janardhanam, V.A. et al. Pre-Clinical Analysis of Changes in Intra-cellular Biochemistry of Glioblastoma Multiforme (GBM) Cells Due to c-Myc Silencing. Cell Mol Neurobiol 34, 1059–1069 (2014). https://doi.org/10.1007/s10571-014-0083-4
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DOI: https://doi.org/10.1007/s10571-014-0083-4