4-Acetylantroquinonol B inhibits colorectal cancer tumorigenesis and suppresses cancer stem-like phenotype

Tung Cheng Chang, Chi-Tai Yeh, Bamodu Oluwaseun Adebayo, Ying-Chin Lin, Li Deng, Yerra Koteswara Rao, Chun Chih Huang, Wei Hwa Lee, Alexander T H Wu, Michael Hsiao, Chih Hsiung Wu, Liang Shun Wang, Yew Min Tzeng

研究成果: 雜誌貢獻文章

20 引文 斯高帕斯(Scopus)

摘要

4-Acetylantroquinonol B (4-AAQB), closely related to the better known antroquinonol, is a bioactive isolate of the mycelia of Antrodia camphorata, a Taiwanese mushroom with documented anti-inflammatory, hypoglycemic, vasorelaxative, and recently demonstrated, antiproliferative activity. Based on its traditional use, we hypothesized that 4-AAQB may play an active role in the suppression of cellular transformation, tumor aggression and progression, as well as chemoresistance in colorectal carcinoma (CRC). In this study, we investigated the antiproliferative role of 4-AAQB and its underlying molecular mechanism. We also compared its anticancer therapeutic potential with that of antroquinonol and the CRC combination chemotherapy of choice - folinic acid, fluorouracil and oxaliplatin (FOLFOX). Our results showed that 4-AAQB was most effective in inhibiting tumor proliferation, suppressing tumor growth and attenuating stemness-related chemoresistance. 4-AAQB negatively regulates vital oncogenic and stem cell maintenance signal transduction pathways, including the Lgr5/Wnt/β-catenin, JAK-STAT, and non-transmembrane receptor tyrosine kinase signaling pathways, as well as inducing a dose-dependent downregulation of ALDH and other stemness related factors. These results were validated in vivo, with animal studies showing 4-AAQB possessed comparable tumor-shrinking ability as FOLFOX and potentiates ability of the later to reduce tumor size. Thus, 4-AAQB, a novel small molecule, projects as a potent therapeutic agent for monotherapy or as a component of standard combination chemotherapy.
原文英語
頁(從 - 到)258-268
頁數11
期刊Toxicology and Applied Pharmacology
288
發行號2
DOIs
出版狀態已發佈 - 十月 15 2015

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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