2. Academic Validation
  3. Avenanthramide A triggers potent ROS-mediated anti-tumor effects in colorectal cancer by directly targeting DDX3

Avenanthramide A triggers potent ROS-mediated anti-tumor effects in colorectal cancer by directly targeting DDX3

  • Cell Death Dis. 2019 Aug 7;10(8):593. doi: 10.1038/s41419-019-1825-5.
Rong Fu 1 2,  Peng Yang 1 2,  Zongwei Li 3,  Wen Liu 1,  Sajid Amin 1,  Zhuoyu Li 4 5
Affiliations

Affiliations

  • 1 Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, 030006, China.
  • 2 Institutes of Biomedical Sciences, Shanxi University, Taiyuan, 030006, China.
  • 3 Department of Lymphoma and Myeloma, Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
  • 4 Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, 030006, China. lzy@sxu.edu.cn.
  • 5 School of Life Science, Shanxi University, Taiyuan, 030006, China. lzy@sxu.edu.cn.
PMID: 31391454 DOI: 10.1038/s41419-019-1825-5
Abstract

Colorectal Cancer (CRC) is a common malignant gastrointestinal tumor with high mortality worldwide. Drug resistance and cytotoxicity to normal cells are the main causes of chemotherapeutic treatment failure in CRC. Therefore, extracting the bioactive compounds from Natural Products with anti-carcinogenic activity and minimal side-effects is a promising strategy against CRC. The present study aims to evaluate the anti-carcinogenic properties of avenanthramides (AVNs) extracted from oats bran and clarify the underlying molecular mechanisms. We demonstrated that AVNs treatment suppressed mitochondrial bioenergetic generation, resulting in mitochondrial swelling and increased Reactive Oxygen Species (ROS) production. Further study indicated that AVNs treatment significantly reduced DDX3 expression, an oncogenic RNA helicase highly expressed in human CRC tissues. DDX3 overexpression reversed the ROS-mediated CRC Apoptosis induced by AVNs. Of note, we identified Avenanthramide A (AVN A) as the effective ingredient in AVNs extracts. AVN A blocked the ATPase activity of DDX3 and induced its degradation by directly binding to the Arg287 and Arg294 residues in DDX3. In conclusion, these innovative findings highlight that AVNs extracts, in particular its bioactive compound AVN A may crack the current hurdles in the way of CRC treatment.

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