Inhibition of AP-1 and neoplastic transformation by fresh apple peel extract

被引:42
作者
Ding, M [1 ]
Lu, YJ
Bowman, L
Huang, CS
Leonard, S
Wang, LY
Vallyathan, V
Castranova, V
Shi, XL
机构
[1] NIOSH, Pathol & Physiol Res Branch, Hlth Effects Lab Div, Morgantown, WV 26505 USA
[2] NYU, Sch Med, Nelson Inst Environm Med, Tuxedo Pk, NY 10987 USA
关键词
D O I
10.1074/jbc.M311465200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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(radical anion)) 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.
引用
收藏
页码:10670 / 10676
页数:7
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