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Novel Antrodia cinnamomea Extract Reduced Cancer Stem-Like Phenotype Changes and Resensitized KRAS-Mutant Colorectal Cancer via a MicroRNA-27a Pathway

1
Program in Pharmacology and Toxicology, Department of Medicine, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan
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Cardiovascular Research Center, Buddhist Tzu Chi General Hospital, Hualien 97004, Taiwan
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Department of Pharmacology, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan
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Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan
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Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan
6
Oneness Biotech Company, Ltd., Taipei 10680, Taiwan
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(11), 1657; https://doi.org/10.3390/cancers11111657
Received: 20 September 2019 / Revised: 14 October 2019 / Accepted: 23 October 2019 / Published: 26 October 2019
Colorectal cancer (CRC) is one of the most common causes of death in Taiwan. Previous studies showed that Antrodia cinnamomea (AC) can treat poisoning, diarrhea, and various types of cancer. Therefore, we purified a novel ubiquinone derivative, AC009, and investigated its antitumor effects. Cell viability assays revealed that AC009 reduced the viability of several human CRC cell lines. AC009 treatment resulted in cell-cycle arrest/apoptosis, and these effects may occur via caspase and Bcl-2 signaling pathways. We demonstrated that AC009 could significantly inhibit in vivo tumor growth in xenograft mouse models. Using messenger RNA (mRNA) and microRNA (miRNA) microarrays, we found that KRAS gene expression was also regulated by AC009, possibly through specific miRNAs. AC009 also reduced cancer stem-cell marker CD44+/CD24+ expression and restored the tumor inhibition effect of cetuximab in KRAS-mutant CRC. Moreover, we found that miRNA-27a could restore the tumor inhibition effect of cetuximab in KRAS-mutant CRC cells. Taken together, our results suggest that AC009 has therapeutic potential against human wild-type and KRAS-mutant CRC. View Full-Text
Keywords: colorectal cancer; Antrodia cinnamomea; KRAS; resensitization; miRNA-27a colorectal cancer; Antrodia cinnamomea; KRAS; resensitization; miRNA-27a
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Lin, T.-J.; Lai, K.-C.; Lee, A.-S.; Chang, C.-H.; Liu, C.-L.; Chung, C.-H. Novel Antrodia cinnamomea Extract Reduced Cancer Stem-Like Phenotype Changes and Resensitized KRAS-Mutant Colorectal Cancer via a MicroRNA-27a Pathway. Cancers 2019, 11, 1657.

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