Inhibition of AP-1 and neoplastic transformation by fresh apple peel extract.
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 (O(2)(-)) 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.
Ding
Min
M
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA. mid5@cdc.gov
Lu
Yongju
Y
Bowman
Linda
L
Huang
Chuanshu
C
Leonard
Stephen
S
Wang
Liying
L
Vallyathan
Val
V
Castranova
Vince
V
Shi
Xianglin
X
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004578:Electron Spin Resonance Spectroscopy; D017930:Genes, Reporter; D006861:Hydrogen Peroxide / Q000737:chemistry; D017665:Hydroxyl Radical; D008156:Luciferases / Q000378:metabolism; D027845:Malus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010766:Phosphorylation; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D013481:Superoxides; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015533:Transcriptional Activation; D019076:Transgenes; D014466:Ultraviolet Rays
D002273:Carcinogens; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D013481:Superoxides; D017665:Hydroxyl Radical; D015127:9,10-Dimethyl-1,2-benzanthracene; D006861:Hydrogen Peroxide; D008156:Luciferases; D013755:Tetradecanoylphorbol Acetate