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Journal of Environmental Pathology, Toxicology and Oncology
IF: 1.625 5-Year IF: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Print: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2019031445
pages 13-21

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

Huazhi Zhang
Department of Medical Oncology, Affiliated Jinan Third Hospital of Jining Medical University, Jinan, Shandong Province, 250132, China
Ping Lv
Department of Hematology, The Fourth People's Hospital of Jinan City, Jinan, Shandong Province, 250031, China
Zhanzhan Xiao
Department of Emergency Services, The Fourth People's Hospital of Jinan City, Jinan, Shandong Province, 250031, China
Elamaran Ananda Jothi
CAS in Marine Biology, Faculty of Marine Sciences, Annamalai University, Parangipettai, India 608502
Jiangfei Yang
Department of Medical Imaging, Shandong Provincial Hospital Affiliated with Shandong University, Huaiyin District, Jinan, Shandong 250021, People's Republic of China

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.

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