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Open AccessArticle

Effect of Nicotine on CYP2B1 Expression in a Glioma Animal Model and Analysis of CYP2B6 Expression in Pediatric Gliomas

1
Departamento de Inmunobioquímica, Instituto Nacional de Perinatología IER, Secretaría de Salud, 11000 Ciudad de México, Mexico
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Laboratorio de Bioquímica-Genética, Instituto Nacional de Pediatría, Secretaría de Salud, 04530 Ciudad de México, Mexico
3
CONACyT—Instituto Nacional de Pediatría, Secretaría de Salud, 04530 Ciudad de México, Mexico
4
Departamento de Neurocirugía, Instituto Nacional de Pediatría, Secretaría de Salud, 04530 Ciudad de México, Mexico
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Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Secretaría de Salud, 04530 Ciudad de México, Mexico
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Departamento de Probabilidad y Estadística, Instituti de Investigaciones en Matemáticas Aplicadas y en Sistemas, UNAM, 04510 Ciudad de México, Mexico
7
Laboratorio de Neurociencias, Instituto Nacional de Pediatría, Secretaría de Salud, 04530 Ciudad de México, Mexico
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(6), 1790; https://doi.org/10.3390/ijms19061790
Received: 30 April 2018 / Revised: 12 June 2018 / Accepted: 13 June 2018 / Published: 16 June 2018
(This article belongs to the Special Issue Cytochromes P450: Drug Metabolism and Bioactivation)
Cyclophosphamide (CPA) is a pro-drug commonly used in the chemotherapeutic schemes for glioma treatment but has high toxicity and the side effects include brain damage and even death. Since CPA is activated mainly by CY2B6, over-expression of the enzyme in the tumor cells has been proposed to enhance CPA activation. In this study, we explored the induction of the Cyp2b1 (homologous to CYP2B6) by nicotine in an animal rat model with glioma. Gene expression and protein levels were analyzed by RT-PCR and Western blot. Nicotine treatment increased CYP2B1 protein levels in the healthy animals’ brain tissue. In the brain tissue of animals with glioma, the CYP2B1 showed a high expression, even before nicotine treatment. Nicotine did not increase significantly the CYP2B1 protein expression in the tumor, but increased its expression in the tumor vicinity, especially around blood vessels in the cortex. We also explored CY2B6 expression in glioma samples derived from pediatric patients. Tumor tissue showed a variable expression of the enzyme, which could depend on the tumor malignancy grade. Induction of the CYP2B6 in pediatric gliomas with lower expression of the enzyme, could be an alternative to improve the antitumoral effect of CPA treatment. View Full-Text
Keywords: CYP2B6; CYP2B1; glioma; cyclophosphamide; pediatric; brain CYP2B6; CYP2B1; glioma; cyclophosphamide; pediatric; brain
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Nava-Salazar, S.; Gómez-Manzo, S.; Marcial-Quino, J.; Marhx-Bracho, A.; Phillips-Farfán, B.V.; Diaz-Avalos, C.; Vanoye-Carlo, A. Effect of Nicotine on CYP2B1 Expression in a Glioma Animal Model and Analysis of CYP2B6 Expression in Pediatric Gliomas. Int. J. Mol. Sci. 2018, 19, 1790.

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