Phenolic compounds stage an interplay between the ubiquitin-proteasome system and ubiquitin signal autophagic degradation for the ubiquitin-based cancer chemoprevention

Tsui Ling Chang, Hung Yu Chiang, Jia Yi Shen, Shu Wei Lin, Pei-Jane Tsai

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Inhibiting proteasome functional insufficiency plays an essential role in cancer prevention. Alternative strategies to target ubiquitin enzymes and ubiquitin-signal autophagic degradation can be the potential treatments. Phenolic compounds demonstrated anti-cancer effects. Phenolic compounds not only effectively inhibit E1, deubiquitinating enzyme, and 26S activity but also induce apoptosis in A549 cells. The IC50 of 26S activity and LD50 of A549 cells were nearly equivalent. Therefore, apoptosis may occur via the inhibition of the 26S proteasome activity. Inhibition of the proteasome by tannic acid in A549 cells resulted in reduction of S5a and 20S, accumulation of ubiquitin, and degradation of PARP, followed by induction of apoptosis. USP15 may play an essential role in the stability and activity of caspase-3. The levels of S5a, USP15 and USP47 were regulated by phenolic compounds, and the levels of procaspase-3 and polyADP-ribose polymerase were also decreased in A549 cells treated with phenolic compounds. Interestingly, tannic acid decreased Ub-conjugates while M + G + E increased the accumulation of Ub-conjugates in A549 reporter cells, whereas ubiquitin, E1, and USP47 levels were low in M + G + E-treated A549 reporter cells at 24 hours. Taken together, phenolic compounds may play an important role in mediating apoptosis by regulating the ubiquitin-proteasome pathway and autophagy system.

Original languageEnglish
Pages (from-to)857-871
Number of pages15
JournalJournal of Functional Foods
Volume17
DOIs
Publication statusPublished - 2015 Aug 1

All Science Journal Classification (ASJC) codes

  • Food Science
  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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