Significant Lower Carboxylesterase Specific Activity in Meningiomas and Gliomas and Derived Primary Cell Culture Indicate Reduction in Anticancer Drug Metabolism

Abstract

Aims: Carboxylesterases (CE) convert carboxylic esters to alcohols and carboxylic acids. CE is a protective factor in the brain cells categorized as phase-I drug-metabolizing enzymes. Therefore we aim to find out the difference CE specific activity for Brain tumors as compared to the normal brain to understand the drug metabolism efficiency. Study Design: Total Protein and Carboxylesterase assays were performed for Meningiomas and gliomas and derived primary cell culture. Place and Duration of Study: Sample: Department of Neurosurgery (Neuro center) and Department of Neuropathology, Experiments performed: Departments of Neurochemistry and Neurovirology, NIMHANS, Bangalore, between January 2001 and October 2005. Methodology: CE spectrophotometric assays were studied for 30 meningiomas and 52 gliomas in 82 males, while 45 meningiomas and 29 gliomas in 74 females respectively and derived cell culture. The brain tumor protein band pattern was studied by electrophoresis. Results: The brain tissue extracts for SDS PAGE displayed a high intense single protein (not purified) band of 60 kDa in brain tumors as compared to normal brain. The similar CE-specific activity between the meningiomas 20.96±5.071 (n=50) and gliomas 20.77±4.4644 nmol/min/mg (n=61) respectively, exhibited significantly lower CE activity as compared to normal Brain (n=106) 52.355 ± 11.15 nmol/min/mg of protein and p-value was less than 0.0001 extremely statistically significant. Hence CE activities are significantly lower in all grades of parent Brain tumors as compared to normal brain. Primary cell cultures with respective passages expressed lower CE activities than parent tumors respectively. Conclusions: The current results indicate the reason for the failure of anticancer drug metabolism efficiency for both meningiomas and gliomas due to one of the reasons for exhibiting lower CE-specific activity. The chance of solving the drug metabolism provided by the current study helps advanced molecular biochemistry in designing drug conjugates for efficient metabolism by CE-specific activity and monitoring the chemotherapy for anticancer drug therapeutics in the future.