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Toxicol Appl Pharmacol. 2015 Oct 15;288(2):258-68. doi: 10.1016/j.taap.2015.07.025. Epub 2015 Jul 30.

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

Author information

1
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Department of Surgery, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan.
2
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Department of Surgery, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan; Department of Medical Research and Education, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan.
3
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Department of Medical Research and Education, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan.
4
Department of Family Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
5
Beijing Bioprocess Key Laboratory, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China; Amoy-BUCT Industrial Bio-technovation Institute, Amoy 361022, China.
6
Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Taichung 41349, Taiwan.
7
Department of Pathology, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan.
8
Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
9
Genomics Research Center, Academia Sinica, Taipei, Taiwan.
10
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Department of Surgery, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan; Department of Medical Research and Education, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan. Electronic address: wangls72269@yahoo.com.tw.
11
Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Taichung 41349, Taiwan. Electronic address: ymtzeng@cyut.edu.tw.

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.

KEYWORDS:

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

PMID:
26235807
DOI:
10.1016/j.taap.2015.07.025
[Indexed for MEDLINE]

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