title: Apigenin inhibits COX-2, PGE2, and EP1 and also initiates terminal differentiation in the epidermis of tumor bearing mice.
abstract: Non-melanoma skin cancer (NMSC) is the most prevalent cancer in the United States. NMSC overexpresses cyclooxygenase-2 (COX-2). COX-2 synthesizes prostaglandins such as PGE2 which promote proliferation and tumorigenesis by engaging G-protein-coupled prostaglandin E receptors (EP). Apigenin is a bioflavonoid that blocks mouse skin tumorigenesis induced by the chemical carcinogens, 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the effect of apigenin on the COX-2 pathway has not been examined in the DMBA/TPA skin tumor model. In the present study, apigenin decreased tumor multiplicity and incidence in DMBA/TPA-treated SKH-1 mice. Analysis of the non-tumor epidermis revealed that apigenin reduced COX-2, PGE2, EP1, and EP2 synthesis and also increased terminal differentiation. In contrast, apigenin did not inhibit the COX-2 pathway or promote terminal differentiation in the tumors. Since fewer tumors developed in apigenin-treated animals which contained reduced epidermal COX-2 levels, our data suggest that apigenin may avert skin tumor development by blocking COX-2.
authors.affiliation: Department of Pharmacology & Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Kiraly
authors.affiliation: Department of Pharmacology & Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: Eman
authors.initials: E
authors.lastname: Soliman
authors.affiliation: Department of Comparative Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Jenkins
authors.affiliation: Department of Pharmacology & Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC, USA. Electronic address: vandrossr@ecu.edu.
authors.forename: Rukiyah T
authors.initials: RT
authors.lastname: Van Dross
mesh_terms: D000818:Animals; D047310:Apigenin / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D051379:Mice; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000378:metabolism*; D012878:Skin Neoplasms / Q000188:drug therapy
chemical_list: C545636:Ptger1 protein, mouse; D058306:Receptors, Prostaglandin E, EP1 Subtype; D047310:Apigenin; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: Apigenin; COX-2; Differentiation; EP1; Proliferation; Skin cancer