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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)258-268
Number of pages11
JournalToxicology and Applied Pharmacology
Volume288
Issue number2
DOIs
Publication statusPublished - Oct 15 2015

Fingerprint

Colorectal Neoplasms
Carcinogenesis
oxaliplatin
Phenotype
Tumors
Neoplasms
Aptitude
Chemotherapy
Leucovorin
Combination Drug Therapy
Fluorouracil
Antrodia
Catenins
Signal transduction
Agaricales
Mycelium
Receptor Protein-Tyrosine Kinases
4-acetylantroquinonol B
Stem cells
Aggression

Keywords

  • 4-Acetylantroquinonol B
  • Antrodia camphorata
  • Cancer progression
  • Cancer stem cells
  • Chemotherapy
  • Colorectal cancer

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

4-Acetylantroquinonol B inhibits colorectal cancer tumorigenesis and suppresses cancer stem-like phenotype. / Chang, Tung Cheng; Yeh, Chi-Tai; Adebayo, Bamodu Oluwaseun; Lin, Ying-Chin; Deng, Li; Rao, Yerra Koteswara; Huang, Chun Chih; Lee, Wei Hwa; Wu, Alexander T H; Hsiao, Michael; Wu, Chih Hsiung; Wang, Liang Shun; Tzeng, Yew Min.

In: Toxicology and Applied Pharmacology, Vol. 288, No. 2, 15.10.2015, p. 258-268.

Research output: Contribution to journalArticle

Chang, Tung Cheng ; Yeh, Chi-Tai ; Adebayo, Bamodu Oluwaseun ; Lin, Ying-Chin ; Deng, Li ; Rao, Yerra Koteswara ; Huang, Chun Chih ; Lee, Wei Hwa ; Wu, Alexander T H ; Hsiao, Michael ; Wu, Chih Hsiung ; Wang, Liang Shun ; Tzeng, Yew Min. / 4-Acetylantroquinonol B inhibits colorectal cancer tumorigenesis and suppresses cancer stem-like phenotype. In: Toxicology and Applied Pharmacology. 2015 ; Vol. 288, No. 2. pp. 258-268.
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