Origanum majorana Ethanolic Extract Promotes Colorectal Cancer Cell Death by Triggering Abortive Autophagy and Activation of the Extrinsic Apoptotic Pathway
Identifieur interne : 000B56 ( Main/Exploration ); précédent : 000B55; suivant : 000B57Origanum majorana Ethanolic Extract Promotes Colorectal Cancer Cell Death by Triggering Abortive Autophagy and Activation of the Extrinsic Apoptotic Pathway
Auteurs : Nehla Benhalilou [Émirats arabes unis] ; Halima Alsamri [Émirats arabes unis] ; Aysha Alneyadi [Émirats arabes unis] ; Khawlah Athamneh [Émirats arabes unis] ; Asma Alrashedi [Émirats arabes unis] ; Nedaa Altamimi [Émirats arabes unis] ; Yusra Al Dhaheri [Émirats arabes unis] ; Ali H. Eid [Liban] ; Rabah Iratni [Émirats arabes unis]Source :
- Frontiers in Oncology [ 2234-943X ] ; 2019.
Abstract
Colorectal cancer is considered as the third leading cause of cancer death. In the present study, we investigated the potential anticancer effect and the molecular mechanism of
Url:
DOI: 10.3389/fonc.2019.00795
PubMed: 31497536
PubMed Central: 6712482
Affiliations:
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xml:lang="en" level="a" type="main"><italic>Origanum majorana</italic> Ethanolic Extract Promotes Colorectal Cancer Cell Death by Triggering Abortive Autophagy and Activation of the Extrinsic Apoptotic Pathway</title><author><name sortKey="Benhalilou, Nehla" sort="Benhalilou, Nehla" uniqKey="Benhalilou N" first="Nehla" last="Benhalilou">Nehla Benhalilou</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Biology, College of Science, United Arab Emirates University</institution>,<addr-line>Abu Dhabi</addr-line>,<country>United Arab Emirates</country></nlm:aff><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alsamri, Halima" sort="Alsamri, Halima" uniqKey="Alsamri H" first="Halima" last="Alsamri">Halima Alsamri</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Biology, College of Science, United Arab Emirates University</institution>,<addr-line>Abu Dhabi</addr-line>,<country>United Arab Emirates</country></nlm:aff><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alneyadi, Aysha" sort="Alneyadi, Aysha" uniqKey="Alneyadi A" first="Aysha" last="Alneyadi">Aysha Alneyadi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Biology, College of Science, United Arab Emirates University</institution>,<addr-line>Abu Dhabi</addr-line>,<country>United Arab Emirates</country></nlm:aff><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Athamneh, Khawlah" sort="Athamneh, Khawlah" uniqKey="Athamneh K" first="Khawlah" last="Athamneh">Khawlah Athamneh</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Biology, College of Science, United Arab Emirates University</institution>,<addr-line>Abu Dhabi</addr-line>,<country>United Arab Emirates</country></nlm:aff><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alrashedi, Asma" sort="Alrashedi, Asma" uniqKey="Alrashedi A" first="Asma" last="Alrashedi">Asma Alrashedi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Biology, College of Science, United Arab Emirates University</institution>,<addr-line>Abu Dhabi</addr-line>,<country>United Arab Emirates</country></nlm:aff><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Altamimi, Nedaa" sort="Altamimi, Nedaa" uniqKey="Altamimi N" first="Nedaa" last="Altamimi">Nedaa Altamimi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Biology, College of Science, United Arab Emirates University</institution>,<addr-line>Abu Dhabi</addr-line>,<country>United Arab Emirates</country></nlm:aff><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Al Dhaheri, Yusra" sort="Al Dhaheri, Yusra" uniqKey="Al Dhaheri Y" first="Yusra" last="Al Dhaheri">Yusra Al Dhaheri</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Biology, College of Science, United Arab Emirates University</institution>,<addr-line>Abu Dhabi</addr-line>,<country>United Arab Emirates</country></nlm:aff><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Eid, Ali H" sort="Eid, Ali H" uniqKey="Eid A" first="Ali H." last="Eid">Ali H. Eid</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut</institution>,<addr-line>Beirut</addr-line>,<country>Lebanon</country></nlm:aff><country xml:lang="fr">Liban</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Iratni, Rabah" sort="Iratni, Rabah" uniqKey="Iratni R" first="Rabah" last="Iratni">Rabah Iratni</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Biology, College of Science, United Arab Emirates University</institution>,<addr-line>Abu Dhabi</addr-line>,<country>United Arab Emirates</country></nlm:aff><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Frontiers in Oncology</title><idno type="eISSN">2234-943X</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>Colorectal cancer is considered as the third leading cause of cancer death. In the present study, we investigated the potential anticancer effect and the molecular mechanism of <italic>Origanum majorana</italic> ethanolic extract (OME) against human colorectal cancer cells. We showed that OME exhibited strong anti-proliferative activity in a concentration- and time-dependent manner against two human colorectal cancer cell lines (HT-29 and Caco-2). OME inhibited cell viability, colony growth and induced mitotic arrest of HT-29 cells. Also, OME induced DNA damage, triggered abortive autophagy and activated a caspase 3 and 7-dependent extrinsic apoptotic pathway, most likely through activation of the TNFα pathway. Time-course analysis revealed that DNA damage occurred concomitantly with abortive autophagy after 4 h post-OME treatment while apoptosis was activated only 24 h later. Blockade of autophagy initiation, by 3-methyladenine, partially rescued OME-induced cell death. Cell viability arose from 37% in control group to 67% in group pre-treated with 3-MA before addition of OME. Inhibition of apoptosis, however, had a minimal effect on cell viability; it rose from 37% in control group to 43% in group pre-treated with Z-VAD-FMK. We also found that OME downregulated survivin in HT-29 cells. Our findings provide a strong evidence that <italic>O. majorana</italic> extract possesses strong anti-colon cancer potential, at least, through induction of autophagy and apoptosis. These finding provide the basis for therapeutic potential of <italic>O. majorana</italic> in the treatment of colon cancer.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Pecorino, L" uniqKey="Pecorino L">L Pecorino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Newman, Dj" uniqKey="Newman D">DJ Newman</name></author><author><name sortKey="Cragg, Gm" uniqKey="Cragg G">GM Cragg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goel, P" uniqKey="Goel P">P Goel</name></author><author><name sortKey="Vasudeva, N" uniqKey="Vasudeva N">N Vasudeva</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leeja, L" uniqKey="Leeja L">L Leeja</name></author><author><name sortKey="Thoppil, Je" uniqKey="Thoppil J">JE Thoppil</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yazdanparast, 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first="Yusra" last="Al Dhaheri">Yusra Al Dhaheri</name><name sortKey="Alneyadi, Aysha" sort="Alneyadi, Aysha" uniqKey="Alneyadi A" first="Aysha" last="Alneyadi">Aysha Alneyadi</name><name sortKey="Alrashedi, Asma" sort="Alrashedi, Asma" uniqKey="Alrashedi A" first="Asma" last="Alrashedi">Asma Alrashedi</name><name sortKey="Alsamri, Halima" sort="Alsamri, Halima" uniqKey="Alsamri H" first="Halima" last="Alsamri">Halima Alsamri</name><name sortKey="Altamimi, Nedaa" sort="Altamimi, Nedaa" uniqKey="Altamimi N" first="Nedaa" last="Altamimi">Nedaa Altamimi</name><name sortKey="Athamneh, Khawlah" sort="Athamneh, Khawlah" uniqKey="Athamneh K" first="Khawlah" last="Athamneh">Khawlah Athamneh</name><name sortKey="Iratni, Rabah" sort="Iratni, Rabah" uniqKey="Iratni R" first="Rabah" last="Iratni">Rabah Iratni</name></country><country name="Liban"><noRegion><name sortKey="Eid, Ali H" sort="Eid, Ali H" uniqKey="Eid A" first="Ali H." last="Eid">Ali H. 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