Avenanthramide A triggers potent ROS-mediated anti-tumor effects in colorectal cancer by directly targeting DDX3
Identifieur interne : 000A19 ( Main/Exploration ); précédent : 000A18; suivant : 000A20Avenanthramide A triggers potent ROS-mediated anti-tumor effects in colorectal cancer by directly targeting DDX3
Auteurs : Rong Fu [République populaire de Chine] ; Peng Yang [République populaire de Chine] ; Zongwei Li [États-Unis] ; Wen Liu [République populaire de Chine] ; Sajid Amin [République populaire de Chine] ; Zhuoyu Li [République populaire de Chine]Source :
- Cell Death & Disease [ 2041-4889 ] ; 2019.
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.
Url:
DOI: 10.1038/s41419-019-1825-5
PubMed: 31391454
PubMed Central: 6685981
Affiliations:
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Zhuoyu" uniqKey="Li Z" first="Zhuoyu" last="Li">Zhuoyu Li</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 2008</institution-id><institution-id institution-id-type="GRID">grid.163032.5</institution-id><institution>Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education,</institution><institution>Shanxi University,</institution></institution-wrap>Taiyuan, 030006 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Taiyuan</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 2008</institution-id><institution-id institution-id-type="GRID">grid.163032.5</institution-id><institution>School of Life Science,</institution><institution>Shanxi University,</institution></institution-wrap>Taiyuan, 030006 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Taiyuan</wicri:regionArea></affiliation></author></analytic><series><title level="j">Cell Death & Disease</title><idno type="eISSN">2041-4889</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Brenner, H" uniqKey="Brenner H">H Brenner</name></author><author><name sortKey="Kloor, M" uniqKey="Kloor M">M Kloor</name></author><author><name sortKey="Pox, Cp" uniqKey="Pox C">CP Pox</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shanmugam, Mk" uniqKey="Shanmugam M">MK Shanmugam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, X" uniqKey="Yu X">X Yu</name></author><author><name sortKey="Yang, M" uniqKey="Yang M">M Yang</name></author><author><name sortKey="Dong, J" uniqKey="Dong J">J Dong</name></author><author><name sortKey="Shen, R" uniqKey="Shen R">R Shen</name></author></analytic></biblStruct><biblStruct><analytic><author><name 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Sajid" uniqKey="Amin S" first="Sajid" last="Amin">Sajid Amin</name><name sortKey="Fu, Rong" sort="Fu, Rong" uniqKey="Fu R" first="Rong" last="Fu">Rong Fu</name><name sortKey="Li, Zhuoyu" sort="Li, Zhuoyu" uniqKey="Li Z" first="Zhuoyu" last="Li">Zhuoyu Li</name><name sortKey="Li, Zhuoyu" sort="Li, Zhuoyu" uniqKey="Li Z" first="Zhuoyu" last="Li">Zhuoyu Li</name><name sortKey="Liu, Wen" sort="Liu, Wen" uniqKey="Liu W" first="Wen" last="Liu">Wen Liu</name><name sortKey="Yang, Peng" sort="Yang, Peng" uniqKey="Yang P" first="Peng" last="Yang">Peng Yang</name><name sortKey="Yang, Peng" sort="Yang, Peng" uniqKey="Yang P" first="Peng" last="Yang">Peng Yang</name></country><country name="États-Unis"><region name="Texas"><name sortKey="Li, Zongwei" sort="Li, Zongwei" uniqKey="Li Z" first="Zongwei" last="Li">Zongwei Li</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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