Nobiletin Attenuates Cell Proliferation by Modulating the Activating Protein-1 Signaling Pathway in 7,12-Dimethylbenz[a]anthracene-Induced Mammary Carcinogenesis.

Abstract

Breast cancer is a widespread disease that affects women globally. Diagnostic processes and remedial approaches to breast carcinogenesis have improved in recent decades, but continuous survival of patients with breast carcinogenesis is still lacking due to increased cell proliferation. The aim of the present work is to explore the anticell proliferative effects of nobiletin (NOB) against 7,12-dimethylbenz[a]anthracene (DMBA)-treated mammary tumorigenesis in rats. We stimulate mammary carcinogenesis using oral gavage of DMBA (25 mg/kg body weight) mixed with olive oil (1 mL). This results in reduced body weight; increased liver marker enzymes such as alkaline phosphatase, acid phosphatase, aspartate aminotransferase, and alanine aminotransferase; and cell proliferative markers such as c-Jun, proliferating cell nuclear antigen, c-Fos, cyclin D1, and activating protein-1 (AP-1) in the DMBA-treated cancer-bearing animals. NOB administration improved body weight, significantly reduced hepatic marker enzymes, and altered histopathological changes. Furthermore, NOB efficiently reduced tumor cell proliferation markers in DMBA-induced mammary carcinogenesis. Overall, these results suggest that NOB has an anticell proliferative effect on DMBA-induced mammary cancer via modulation of the AP-1 signaling pathway.