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 in | Toxicology and applied pharmacology Vol. 288; no. 2; pp. 258 - 268 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
15.10.2015
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Subjects | |
Online Access | Get full text |
ISSN | 0041-008X 1096-0333 |
DOI | 10.1016/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.
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•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. |
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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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Keywords | Cancer progression Chemotherapy 4-Acetylantroquinonol B Cancer stem cells Antrodia camphorata Colorectal cancer |
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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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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 |
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