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

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...

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Published inToxicology and applied pharmacology Vol. 288; no. 2; pp. 258 - 268
Main Authors 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
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 15.10.2015
Subjects
Online AccessGet full text
ISSN0041-008X
1096-0333
DOI10.1016/j.taap.2015.07.025

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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. [Display omitted] •4-Acetylantroquinonol B (4-AAQB) suppressed tumor cell proliferation.•4-AAQB regulates oncogenic and stem cell maintenance signal pathways.•4-AAQB negatively regulates Lgr5/Wnt/β-catenin and JAK–STAT pathways.•4-AAQB reduced ALDH and other stemness related factor expression.•In vivo, 4-AAQB has comparable tumor-shrinking ability as FOLFOX.
AbstractList 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/ beta -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.
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.
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. - Highlights: • 4-Acetylantroquinonol B (4-AAQB) suppressed tumor cell proliferation. • 4-AAQB regulates oncogenic and stem cell maintenance signal pathways. • 4-AAQB negatively regulates Lgr5/Wnt/β-catenin and JAK–STAT pathways. • 4-AAQB reduced ALDH and other stemness related factor expression. • In vivo, 4-AAQB has comparable tumor-shrinking ability as FOLFOX.
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. [Display omitted] •4-Acetylantroquinonol B (4-AAQB) suppressed tumor cell proliferation.•4-AAQB regulates oncogenic and stem cell maintenance signal pathways.•4-AAQB negatively regulates Lgr5/Wnt/β-catenin and JAK–STAT pathways.•4-AAQB reduced ALDH and other stemness related factor expression.•In vivo, 4-AAQB has comparable tumor-shrinking ability as FOLFOX.
Author Wu, Alexander T.H.
Chang, Tung-Cheng
Adebayo, Bamodu Oluwaseun
Tzeng, Yew-Min
Lee, Wei-Hwa
Wang, Liang-Shun
Yeh, Chi-Tai
Lin, Ying-Chin
Deng, Li
Huang, Chun-Chih
Hsiao, Michael
Rao, Yerra Koteswara
Wu, Chih-Hsiung
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  organization: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
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  fullname: Deng, Li
  organization: Beijing Bioprocess Key Laboratory, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
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  organization: Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Taichung 41349, Taiwan
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  fullname: Lee, Wei-Hwa
  organization: Department of Pathology, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan
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  givenname: Alexander T.H.
  surname: Wu
  fullname: Wu, Alexander T.H.
  organization: Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
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  organization: Genomics Research Center, Academia Sinica, Taipei, Taiwan
– sequence: 11
  givenname: Chih-Hsiung
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  fullname: Wu, Chih-Hsiung
  organization: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
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  givenname: Liang-Shun
  surname: Wang
  fullname: Wang, Liang-Shun
  email: wangls72269@yahoo.com.tw
  organization: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
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  givenname: Yew-Min
  orcidid: 0000-0002-9360-2072
  surname: Tzeng
  fullname: Tzeng, Yew-Min
  email: ymtzeng@cyut.edu.tw
  organization: Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Taichung 41349, Taiwan
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Issue 2
Keywords Cancer progression
Chemotherapy
4-Acetylantroquinonol B
Cancer stem cells
Antrodia camphorata
Colorectal cancer
Language English
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Snippet 4-Acetylantroquinonol B (4-AAQB), closely related to the better known antroquinonol, is a bioactive isolate of the mycelia of Antrodia camphorata, a Taiwanese...
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StartPage 258
SubjectTerms 4-Acetylantroquinonol B
4-Butyrolactone - analogs & derivatives
4-Butyrolactone - pharmacology
60 APPLIED LIFE SCIENCES
Animals
Antineoplastic Agents, Phytogenic - pharmacology
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Antrodia camphorata
Cancer progression
Cancer stem cells
CARCINOMAS
CELL PROLIFERATION
Cell Proliferation - drug effects
CHEMOTHERAPY
Colorectal cancer
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Cyclohexanones - pharmacology
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm
Fluorouracil - pharmacology
FLUOROURACILS
Gene Expression Regulation, Neoplastic - drug effects
HCT116 Cells
HT29 Cells
Humans
IN VIVO
INFLAMMATION
Leucovorin - pharmacology
MAINTENANCE
Mice, Inbred NOD
Mice, SCID
MUSHROOMS
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Organoplatinum Compounds - pharmacology
PHENOTYPE
PHOSPHOTRANSFERASES
RECEPTORS
Signal Transduction - drug effects
SIGNALS
Spheroids, Cellular
STEM CELLS
Time Factors
Tumor Burden
TUMOR CELLS
TYROSINE
Xenograft Model Antitumor Assays
Title 4-Acetylantroquinonol B inhibits colorectal cancer tumorigenesis and suppresses cancer stem-like phenotype
URI https://dx.doi.org/10.1016/j.taap.2015.07.025
https://www.ncbi.nlm.nih.gov/pubmed/26235807
https://www.proquest.com/docview/1751207696
https://www.osti.gov/biblio/22687786
Volume 288
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