The prognosis of patients with Glioblastoma Multiforme (GBM), the most malignant adult glial brain tumor, remains poor in spite of advances in treatment procedures, including surgical resection, irradiation and chemotherapy. Genetic heterogeneity of GBM warrants extensive studies to gain a thorough understanding of the biology of this tumor. While there have been several studies of global transcript profiling of glioma with the identification of gene signatures for diagnosis and disease management, translation into clinics is yet to happen. In the present study, we report a novel proteomic approach by using two-dimensional difference gel electrophoresis (2D-DIGE) followed by spot picking and analysis of proteins/peptides by Mass Spectrometry. We report Glucose Regulated Protein 78 (GRP78) as a differentially expressed protein in the GBM cell line compared to human normal Astrocyte cells.In addition to proteomic studies, we performed microarray analysis which further confirmed up regulation of GRP78 in GBM cells compared to human normal Astrocyte cells.GRP78 has long been recognized as a molecular chaperone in the endoplasmic reticulum (ER) and can be induced by the ER stress response. Besides its location in the ER, GRP78 has been found in cell plasma membrane, cytoplasm, mitochondria, nucleus and other cellular secretions. GRP78 is implicated in tumor cell proliferation, apoptosis resistance, immune escape, metastasis and angiogenesis, and its elevated expression usually correlates with a variety of tumor micro environmental stresses, including hypoxia, glucose deprivation, lactic acidosis and inflammatory response. GRP78 protein acts as a centrally located sensor of stress, which senses and facilitates the adaptation to the tumor microenvironment.Our findings showed differential expression of this gene in brain cancer GBM and thus confirm similarities in findings in existing transcriptional and translational studies. Thus, these findings could be of further importance for diagnostic, therapeutic and prognostic approaches for dealing with this highly malignant cancer.

Cisplatin, carboplatin, oxaliplatin, and related metallodrugs are extensively being used in the treatment of a variety of cancers. Unfortunately these drugs are highly toxic and tumor becomes drug-resistance. These circumstances have led researchers to look for new cytotoxic agents that may exhibit less toxicity and devoid of drug resistance. It is believed that cisplatin and related drugs directly bind to genomic DNA through purine bases. Synthesis of new metallodrugs which does not follow the above mechanism of action might yield better drugs with less toxicity and devoid of drug resistance. Recently we have demonstrated that several anticancer rhenium compounds do not directly bind to DNA. We have synthesized numerous rhenium pentylcarbonato and acetylsalicylato complexes which include (CO)3(2,2’-Bipyridyl)ReOC(O)OC5H11 (PC-1), (CO)3(1,10-Phenanthroline)ReOC(O)OC5H11 (PC-2), (CO)3(5-Methyl-1,10-Phenanthroline)Re ReOC(O)OC5H11 (PC-3), (CO)3(2,9-Dimethyl-1,10-Phenanthroline)ReOC(O)OC5H11 (PC-4), (CO)3(5,6-Dimethyl-1,10-Phenanthroline)ReOC(O)OC5H11 (PC-5), (CO)3(4,7-Diphenyl-1,10-Phenanthroline)ReOC(O)OC5H11 (PC-6), (CO)3(2,9-Dimethyl-4,7-Diphenyl-1,10-Phenanthroline)Re ReOC(O)OC5H11 (PC-7), (CO)3(2,2’-Bipyridyl)ReOC(O)C6H4·C(O)OCH3 (ASP-1), (CO)3(1,10-Phenanthroline)ReOC(O)C6H4·C(O)OCH3, (ASP-2), (CO)3(5-Methyl-1,10-Phenanthroline)ReOC(O)C6H4·C(O)OCH3 (ASP-3), (CO)3(2,9-Dimethyl-1,10-Phenanthroline)ReOC(O)C6H4·C(O)OCH3 (ASP-4), (CO)3(5,6-Dimethyl-1,10-Phenanthroline)ReOC(O)C6H4·C(O)OCH3 (ASP-5), (CO)3(4,7-Diphenyl-1,10-Phenanthroline)ReOC(O)C6H4·C(O)OCH3 (ASP-6), (CO)3(2,9-Dimethyl-4,7-Diphenyl-1,10-Phenanthroline)ReOC(O)C6H4·C(O)OCH3 (ASP-7). The anticancer properties of the compounds were evaluated using human prostate, alveolar lung, brain, colon, and leukemia cancer cell lines and normal bone marrow cell lines. The results of this study demonstrate that these complexes have significant anticancer properties. Therefore, these complexes can potentially find applications in the treatment of these cancers. Acknowledgment. The work at MSU was partially supported by grants from the National Institutes of Health (Grant No. G11HD038439) and Nuclear Regulatory Commission (Grant No. NRC-HQ-12-G-27-0086). The work at ECSU-UNC was partially supported by grant from the Department of Energy (TMCF/DOE grant). Citation Format: Hirendra N. Banerjee, Deidre Vaughan, Jewe Medley, Gwyn Hyman, Christopher Krauss, Carl Parson, Santosh Mandal, Pola Olczak, Michael Mbagu, Divine Kebulu, Saroj Pramanik, Fazlul Sarkar. Anticancer properties of novel rhenium compounds against human cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4485. doi:10.1158/1538-7445.AM2013-4485