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Published on: December 27, 2016
Inhibition of AP-1 and neoplastic transformation by fresh apple peel extract
Min Ding1, Yongju Lu, Linda Bowman
1Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA. mid5@cdc.gov
Abstract:
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.
Insights
Apple peel extract reduced skin tumors in mice by scavenging free radicals. This extract also blocked key cell signaling pathways involved in tumor promotion, suggesting chemopreventive potential.
Area of Science:
- Oncology
- Dermatology
- Biochemistry
Background:
- Fruit and vegetable consumption is linked to reduced cancer risk.
- Previous research indicates fresh apples may inhibit tumor cell proliferation.
Purpose of the Study:
- To investigate the chemopreventive effects of apple peel extract on skin carcinogenesis.
- To elucidate the mechanisms underlying the potential anti-cancer properties of apple peel extract.
Main Methods:
- Oral administration of apple peel extract to mice initiated with 7,12-dimethylbenz(a)anthracene and promoted with 12-O-tetradecanolyphorbol-13-acetate (TPA).
- Electron Spin Resonance (ESR) analysis to assess radical scavenging activity.
- Mechanistic studies involving JB6 cells and AP-1-luciferase reporter transgenic mice to evaluate inhibition of AP-1 transactivation and MAPK signaling (ERK and JNK).
Main Results:
- Apple peel extract significantly decreased the number of nonmalignant and malignant skin tumors per mouse.
- The extract demonstrated potent scavenging of hydroxyl (OH) and superoxide (O(2)(-)) radicals.
- Pretreatment with apple peel extract inhibited TPA- and ultraviolet B-induced AP-1 transactivation by blocking ERK and JNK activity.
Conclusions:
- Fresh apple peel extract exhibits chemopreventive effects against tumor promoter-induced skin carcinogenesis in mice.
- The observed chemopreventive effects are likely mediated by the extract's antioxidant properties, specifically by inhibiting reactive oxygen species-mediated AP-1 and MAPK pathway activation.
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