Monosodium Glutamate Enhances The Mitogenic And Tumorigenic Potential Of Glioblastoma Cells Through The Stimulation Of Membrane-Bound Complement Regulatory Proteins
Rachael M. Curtis1,2,3, Luma Akil 4, Paul Tchounwou3 and Kenneth Ndebele1,2,3
1Laboratory of Cancer Immunology Target Identification and Validation, Jackson State University, Jackson, Mississippi
2Department of Biology, Jackson State University, Jackson, Mississippi
3College of Science, Engineering and Technology, Jackson State University, Jackson, Mississippi
4School of Public Health, Jackson State University, Jackson, Mississippi
Brain cancers make up approximately 1.4% of all cancer cases and 2.6% of all cancer deaths in the United States and among these cancers, Gliobastoma multiforme (GBM) is the fastest growing, most aggressive. Ranked fourth among cancer deaths in the middle-aged man, GBM is extremely lethal and treatment is often difficult. In fact, patients with GBM usually have a poor prognosis with survival rates lower than 15 months following diagnosis. Although not well-documented, the association between poor diet and GBM has been surmised. Monosodium glutamate (MSG) is a popular flavor enhancer used in the diet. Studies have shown that repeated exposure to MSG is associated with neurotoxicity, however, the specific role of MSG in GBM has not yet been unveiled. Membrane-bound complement regulatory proteins (mCRPs) are over-expressed on the surface of many cancer cells to assist in the evasion of complement-mediated cytotoxicity (CMC). The functional role of mCRPs in MSG-exposed glioblastoma cells has not been investigated. Therefore, the overall goal of this study was to determine the relationship between MSG and mCRPs in glioblastoma cells. This study hypothesized that mCRPs modulate MSG toxicity and enhance the mitogenic and tumorigenic potential of glioblastoma cells. The specific aims of this study were targeted by: (1) assessing the endogenous levels of mCRPs in GBM cell lines through western blot, (2) determining the effect of MSG on the proliferation of GBM cells, using MTS assay, (3) quantifying the levels of mCRP expression in GBM cells exposed to MSG using western blot and densitometry, (4) assessing the proportion of cells in each stage of the cell cycle before and after exposure to MSG using propidium iodine staining and flow cytometry, (5) determining the role of mCRPs and MSG in migration in GBM cell lines using a wound healing assay. Proliferation studies concluded that MSG increases the proliferation of GBM, independent of concentration. Western blot analysis revealed an upregulated level of mCRPs in GBM and an increased expression of mCRPs in MSG-exposed cells. Cell cycle analysis showed an increase in mitotic cells in all GBM, upon MSG stimulation, however, the percentage of cells undergoing apoptosis varied between cell lines and mCRPs. Taken together, these results suggest that MSG exposure stimulates mCRP production in glioblastoma cells, as a mechanism to evade complement mediated cytotoxicity.