Cytochrome P450 1B1, considered as one of the novel chemotherapeutic targets involved in
cancer prevention and
therapy is also associated with the conversion of procarcinogens into their active metabolites. The
aryl hydrocarbon receptor (AhR) is responsible for mediating different
biological responses to a wide variety of
environmental pollutants and also causes transcriptional activation of
cytochrome P450 enzymes including CYP1B1 and thus plays a pivotal role for initiating
cancer and its progression. On the other hand, active carcinogenic metabolites and
reactive oxygen species-mediated stress alter different molecular signalling pathways and gene expressions.
Quinazoline derivatives are recognized for their diversified
biological activities including anticancer properties. The current study was designed for evaluation of chemotherapeutic efficacy of a synthetic
quinazolinone derivative BNUA-3 against
hepatocellular cancer in Sprague-Dawley (SD) rats. A detailed in vivo analysis was performed by administrating BNUA-3 (15, 30 mg/kg b.w. for 28 days, i.p.) in N-Nitrosodiethylamine + 2-
Acetylaminofluorene induced partially hepatectomized
liver cancer in SD rats. This was followed by morphological evaluations, biochemical estimations and analysis of different
mRNA and
protein expressions. The results demonstrated the potency of BNUA-3 in efficient restoration of the altered morphology of liver, its protective effect against lipid peroxidation, enzymic and non-enzymic
antioxidants levels in liver tissue which was disrupted after
cancer induction. The study also demonstrated downregulation of AhR, CYP1B1 and Keap1 expressions with subsequent augmentation of protective Nrf2, HO-1, NQO1 and GSTA1 expressions thus, revealing the chemotherapeutic potency of BNUA-3 in inhibiting liver
carcinogenesis through AhR/CYP1B1/Nrf2/Keap1 pathway.