title: Pre-clinical analysis of changes in intra-cellular biochemistry of glioblastoma multiforme (GBM) cells due to c-Myc silencing.
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.
authors: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, India, dnapolren@gmail.com.
authors: Vishal
authors: V
authors: Rajagopalan
authors: Muthukumar
authors: M
authors: Vaidyanathan
authors: Vanisree Arambakkam
authors: VA
authors: Janardhanam
authors: James E
authors: JE
authors: Bradner
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D006003:Glycogen / Q000378:metabolism; D007150:Immunohistochemistry; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D017208:Rats, Wistar; D016019:Survival Analysis; D014230:Triazoles / Q000494:pharmacology
chemical_list: C561695:(+)-JQ1 compound; D001381:Azepines; D016271:Proto-Oncogene Proteins c-myc; D014230:Triazoles; D006003:Glycogen