5-Demethyltangeretin is more potent than tangeretin in inhibiting dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis

Nianhan Ma, Ching Shu Lai, Chih Han Chung, Jinn-Moon Yang, Kai Cheng Hsu, Chin Yu Chen, Tao Sheng Chung, Shiming Li, Chi Tang Ho, Min Hsiung Pan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

5-Demethyltangeretin (5-DTAN), an autohydrolysis product of tangeretin (TAN) found in citrus peel, exhibited more potent anti-proliferative activity in human cancer cells than TAN itself. In this study, we investigated the anti-tumor promoting effect and underlying molecular mechanism of 5-DTAN on 7,12-dimethyl-benz(a)anthracene (DMBA)-induced and 12-. O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin carcinogenesis. Application of 5-DTAN prior to each TPA-treatment was more effective than that of TAN on reducing the number, incidence and size of papillomas in DMBA-initiated mouse skin. Moreover, 5-DTAN suppressed cyclooxygenase-2 (COX-2) protein expression more strongly than TAN through interfering with phosphatidylinositiol 3-kinase (PI3K)/Akt signaling and further activation of transcription factor NF-κB. Taken together, these results revealed for the first time the in vivo chemopreventive efficacy of 5-DTAN on inhibition of skin carcinogenesis through promoting apoptosis and molecular interactions with residues of PI3K, COX-2, and AKT that may potentially serve as a novel functional agent capable of preventing inflammation-associated tumorigenesis.

Original languageEnglish
Pages (from-to)528-537
Number of pages10
JournalJournal of Functional Foods
Volume11
Issue numberC
DOIs
StatePublished - 1 Jan 2014

Keywords

  • 5-Demethyltangeretin
  • DMBA
  • Inflammation
  • Tangeretin
  • TPA

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