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, our objective is to find out the different CE-specific activity of brain tumors as compared to the normal brain to understand the drug metabolism efficiency.
Background: Carboxylesterase activity can be influenced by
interactions of a variety of compounds either directly or at the level of
enzyme regulation. For e.g. drug elimination decreases and the incidence of
drug-drug interactions increases when two or more drugs compete for hydrolysis
by the same carboxylesterase isozyme.
Materials and Methods: Total Protein and Carboxylesterase assays
were performed for Meningiomas and gliomas and derived primary cell culture.
CE spectrophotometric assays were studied for 30 meningiomas and
52 gliomas in 82 males, while 45 meningiomas and 29 gliomas in 74 female
patients and derived cell culture respectively. The brain tumor protein band
pattern was studied by electrophoresis.
Results: The brain tissue extracts for SDS PAGE displayed a highly
intense single protein (not purified) band of 60 KDa in brain tumors as
compared to normal brains.
The similar CE-specific activity exhibited between the meningiomas
20.96±5.071 (n=50) and gliomas 20.77±4.4644 nmol/min/mg (n=61) respectively
showed 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 brains. Primary cell
cultures with respective passages expressed lower CE activities than parent
tumors respectively. CE activity has to be determined for meningiomas by
comparing them with meninges to understand the efficiency of drug metabolism.
Hence Carboxyl esterase can also be made as biomarkers by developing kits for
diagnosis purposes. Thus the current study promotes applications in the future
by determining tumor and cell culture CE-specific activity for designing
anticancer drugs for efficient metabolism and Targeting.
Conclusions: The current results indicate the reason for the
failure of anticancer drug metabolism efficiency due to lower CE- specific
activity in both meningiomas and gliomas respectively. Advanced molecular
biochemistry and neuropharmacology benefit from the current study's ability to
solve the drug metabolism problem in order to effectively design drug
conjugates for anticancer drug metabolism by CE-specific activity and to
monitor chemotherapy for anticancer drug therapeutics for future clinical
applications.
Author
(s) Details
Prabha
Muddobalaiah
Department of Biotechnology, Ramaiah Institute of Technology,
Bangalore-560054, Karnataka, India.
Vasanthapuram
Ravi
Department of Neurovirology, NIMHANS, Bangalore, India.
Narayana
Swamy Ramachandra Swamy
Department of Biochemistry, Central College, Bangalore University,
Bangalore—560001, India.
Please see the book here:- https://doi.org/10.9734/bpi/prrat/v6/2204
