Inhibition of AP-1 and Neoplastic Transformation by Fresh Apple Peel Extract

• Published in: The Journal of biological chemistry Vol. 279; no. 11; pp. 10670 - 10676
• Main Authors: Ding, Min, Lu, Yongju, Bowman, Linda, Huang, Chuanshu, Leonard, Stephen, Wang, Liying, Vallyathan, Val, Castranova, Vince, Shi, Xianglin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.03.2004; American Society for Biochemistry and Molecular Biology
• Subjects: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Cell Division; Cell Line; Cell Transformation, Neoplastic; Electron Spin Resonance Spectroscopy; Genes, Reporter; Hydrogen Peroxide - chemistry; Hydroxyl Radical; Luciferases - metabolism; Malus - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neoplasms, Experimental - drug therapy; Phosphorylation; Plant Extracts; Reactive Oxygen Species; Signal Transduction; Superoxides; Tetradecanoylphorbol Acetate; Time Factors; Transcription Factor AP-1 - antagonists & inhibitors; Transcription Factor AP-1 - metabolism; Transcriptional Activation; Transgenes; Ultraviolet Rays
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M311465200

Consumption of fruits and vegetables has been associated with a low incidence of cancers and other chronic diseases. Previous studies suggested that fresh apples inhibit tumor cell proliferation. Here we report that oral administration of apple peel extracts decreased the number of nonmalignant and malignant skin tumors per mouse induced by 12-O-tetradecanolyphorbol-13-acetate (TPA) in 7,12-dimethylbenz(a)anthracene-initiated mouse skin. ESR analysis indicated that apple extract strongly scavenged hydroxyl (OH) and superoxide (O2·-) radicals. Mechanistic studies showed that pretreatment with apple peel extract inhibited AP-1 transactivation induced by ultraviolet B irradiation or TPA in JB6 cells and AP-1-luciferase reporter transgenic mice. This inhibitory effect appears to be mediated by the inhibition of ERKs and JNK activity. The results provide the first evidence that an extract from fresh apple peel extract may inhibit tumor promoter-induced carcinogenesis and associated cell signaling, and suggest that the chemopreventive effects of fresh apple may be through its antioxidant properties by blocking reactive oxygen species-mediated AP-1-MAPK activation.