Assessing Nordihydroguaiaretic Acid Therapeutic Effect for Glioblastoma Multiforme

评估去甲二氢愈创木酸对多形性胶质母细胞瘤的治疗效果

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作者:Felicia S Manciu, Jose Guerrero, Kevin E Bennet, Su-Youne Chang, Masum Rahman, Lizbeth V Martinez Lopez, Siobhan Chantigian, Mariana Castellanos, Marian Manciu

Abstract

In this study, we demonstrate that Raman microscopy combined with computational analysis is a useful approach to discriminating accurately between brain tumor bio-specimens and to identifying structural changes in glioblastoma (GBM) bio-signatures after nordihydroguaiaretic acid (NDGA) administration. NDGA phenolic lignan was selected as a potential therapeutic agent because of its reported beneficial effects in alleviating and inhibiting the formation of multi-organ malignant tumors. The current analysis of NDGA's impact on GBM human cells demonstrates a reduction in the quantity of altered protein content and of reactive oxygen species (ROS)-damaged phenylalanine; results that correlate with the ROS scavenger and anti-oxidant properties of NDGA. A novel outcome presented here is the use of phenylalanine as a biomarker for differentiating between samples and assessing drug efficacy. Treatment with a low NDGA dose shows a decline in abnormal lipid-protein metabolism, which is inferred by the formation of lipid droplets and a decrease in altered protein content. A very high dose results in cell structural and membrane damage that favors transformed protein overexpression. The information gained through this work is of substantial value for understanding NDGA's beneficial as well as detrimental bio-effects as a potential therapeutic drug for brain cancer.

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