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

• Published in: International journal of molecular sciences Vol. 19; no. 6; p. 1790
• Main Authors: Nava-Salazar, Sonia, Gómez-Manzo, Saúl, Marcial-Quino, Jaime, Marhx-Bracho, Alfonso, Phillips-Farfán, Bryan V, Diaz-Avalos, Carlos, Vanoye-Carlo, America
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16-06-2018; MDPI
• Subjects: Adolescent; Animals; Blood vessels; brain; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain damage; Brain injury; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell Line, Tumor; Child; Cyclophosphamide; CYP2B1; CYP2B1 protein; CYP2B6; Cytochrome P-450 CYP2B1 - genetics; Cytochrome P-450 CYP2B1 - metabolism; Cytochrome P-450 CYP2B6 - genetics; Cytochrome P-450 CYP2B6 - metabolism; Enzymes; Female; Gene expression; Gene Expression Regulation - drug effects; Glioma; Glioma - genetics; Glioma - metabolism; Glioma - pathology; Homology; Humans; Male; Malignancy; Nicotine; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Overexpression; pediatric; Pediatrics; Polymerase chain reaction; Proteins; Rats; Rats, Inbred F344; Toxicity; Tumor cells; Tumors; CYP2B1; cyclophosphamide; glioma; CYP2B6; brain; pediatric
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19061790

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
(homologous to
) 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.