期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 288, 期 2, 页码 258-268出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2015.07.025
关键词
Antrodia camphorata; 4-Acetylantroquinonol B; Colorectal cancer; Cancer progression; Cancer stem cells; Chemotherapy
资金
- Ministry of Science and Technology of Taiwan [MOST-103-2113-M-324-001-MY2, MOST-104-2811-M-324-001, NSC-101-2314-B-038-010-MY3, MOST-104-2314-B-038-065]
- Taipei Medical University-Shuang Ho Hospital [100TMU-SHH-07, 101TMU-SHH-04]
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 sternness-related chemoresistance. 4-AAQB negatively regulates vital oncogenic and stem cell maintenance signal transduction pathways, including the Lgr5/Wnt/beta-catenin, JAK-STAT, and non-transmembrane receptor tyrosine kinase signaling pathways, as well as inducing a dose-dependent downregulation of ALDH and other sternness 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. (C) 2015 Elsevier Inc. All rights reserved.
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