Ethoxysanguinarine, a Novel Direct Activator of AMP-Activated Protein Kinase, Induces Autophagy and Exhibits Therapeutic Potential in Breast Cancer Cells
Identifieur interne : 000158 ( an2020/Analysis ); précédent : 000157; suivant : 000159Ethoxysanguinarine, a Novel Direct Activator of AMP-Activated Protein Kinase, Induces Autophagy and Exhibits Therapeutic Potential in Breast Cancer Cells
Auteurs : Yuan Si [République populaire de Chine] ; Jiu Wang [République populaire de Chine] ; Xuewen Liu [République populaire de Chine] ; Tong Zhou [République populaire de Chine] ; Yuchen Xiang [République populaire de Chine] ; Te Zhang [République populaire de Chine] ; Xianhui Wang [République populaire de Chine] ; Tingting Feng [République populaire de Chine] ; Li Xu [République populaire de Chine] ; Qingqing Yu [République populaire de Chine] ; Huzi Zhao [République populaire de Chine] ; Ying Liu [République populaire de Chine]Source :
- Frontiers in Pharmacology [ 1663-9812 ] ; 2020.
Abstract
Ethoxysanguinarine (Eth) is a benzophenanthridine alkaloid extracted from
Url:
DOI: 10.3389/fphar.2019.01503
PubMed: 31969821
PubMed Central: 6960228
Affiliations:
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PMC:6960228Le document en format XML
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</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Hubei Key Laboratory of Wudang Local Chinese Medicine Research and Institute of Medicinal Chemistry, Hubei University of Medicine</institution>
,<addr-line>Shiyan</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine</institution>
,<addr-line>Shiyan</addr-line>
,<country>China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Frontiers in Pharmacology</title>
<idno type="eISSN">1663-9812</idno>
<imprint><date when="2020">2020</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Ethoxysanguinarine (Eth) is a benzophenanthridine alkaloid extracted from <italic>Macleaya cordata (Willd) R. Br</italic>
. It possesses antibacterial and antiviral activities and offers therapeutic benefits for the treatment of respiratory syndrome virus-induced cytopathic effects. However, the effect of Eth on human tumors and its pharmacological effects remain to be elucidated, together with its cellular target. Here, we examined the effects of Eth on breast cancer (BC) cells. We found that at low doses, Eth strongly inhibited the viability of BC cell lines and induced autophagy. Mechanistic studies showed that Eth induced autophagy by upregulating the activity of the AMP-activated protein kinase (AMPK). The AMPK inhibitor compound C significantly attenuated Eth-induced autophagy and inhibited proliferation. Meanwhile, the AMPK activator metformin significantly enhanced Eth-induced autophagy and inhibited proliferation. Computational docking and affinity assays showed that Eth directly interacted with the allosteric drug and metabolite site of AMPK to stabilize its activation. AMPK was less activated in tumor samples compared to normal breast tissues and was inversely associated with the prognosis of the patients. Moreover, Eth exhibited potent anti-BC activity in nude mice and favorable pharmacokinetics in rats. These characteristics render Eth as a promising candidate drug for further development and for designing new effective AMPK activators.</p>
</div>
</front>
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</div1>
</back>
</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
</country>
</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Si, Yuan" sort="Si, Yuan" uniqKey="Si Y" first="Yuan" last="Si">Yuan Si</name>
</noRegion>
<name sortKey="Feng, Tingting" sort="Feng, Tingting" uniqKey="Feng T" first="Tingting" last="Feng">Tingting Feng</name>
<name sortKey="Liu, Xuewen" sort="Liu, Xuewen" uniqKey="Liu X" first="Xuewen" last="Liu">Xuewen Liu</name>
<name sortKey="Liu, Xuewen" sort="Liu, Xuewen" uniqKey="Liu X" first="Xuewen" last="Liu">Xuewen Liu</name>
<name sortKey="Liu, Ying" sort="Liu, Ying" uniqKey="Liu Y" first="Ying" last="Liu">Ying Liu</name>
<name sortKey="Liu, Ying" sort="Liu, Ying" uniqKey="Liu Y" first="Ying" last="Liu">Ying Liu</name>
<name sortKey="Liu, Ying" sort="Liu, Ying" uniqKey="Liu Y" first="Ying" last="Liu">Ying Liu</name>
<name sortKey="Liu, Ying" sort="Liu, Ying" uniqKey="Liu Y" first="Ying" last="Liu">Ying Liu</name>
<name sortKey="Si, Yuan" sort="Si, Yuan" uniqKey="Si Y" first="Yuan" last="Si">Yuan Si</name>
<name sortKey="Wang, Jiu" sort="Wang, Jiu" uniqKey="Wang J" first="Jiu" last="Wang">Jiu Wang</name>
<name sortKey="Wang, Jiu" sort="Wang, Jiu" uniqKey="Wang J" first="Jiu" last="Wang">Jiu Wang</name>
<name sortKey="Wang, Xianhui" sort="Wang, Xianhui" uniqKey="Wang X" first="Xianhui" last="Wang">Xianhui Wang</name>
<name sortKey="Xiang, Yuchen" sort="Xiang, Yuchen" uniqKey="Xiang Y" first="Yuchen" last="Xiang">Yuchen Xiang</name>
<name sortKey="Xiang, Yuchen" sort="Xiang, Yuchen" uniqKey="Xiang Y" first="Yuchen" last="Xiang">Yuchen Xiang</name>
<name sortKey="Xu, Li" sort="Xu, Li" uniqKey="Xu L" first="Li" last="Xu">Li Xu</name>
<name sortKey="Yu, Qingqing" sort="Yu, Qingqing" uniqKey="Yu Q" first="Qingqing" last="Yu">Qingqing Yu</name>
<name sortKey="Zhang, Te" sort="Zhang, Te" uniqKey="Zhang T" first="Te" last="Zhang">Te Zhang</name>
<name sortKey="Zhang, Te" sort="Zhang, Te" uniqKey="Zhang T" first="Te" last="Zhang">Te Zhang</name>
<name sortKey="Zhao, Huzi" sort="Zhao, Huzi" uniqKey="Zhao H" first="Huzi" last="Zhao">Huzi Zhao</name>
<name sortKey="Zhao, Huzi" sort="Zhao, Huzi" uniqKey="Zhao H" first="Huzi" last="Zhao">Huzi Zhao</name>
<name sortKey="Zhou, Tong" sort="Zhou, Tong" uniqKey="Zhou T" first="Tong" last="Zhou">Tong Zhou</name>
<name sortKey="Zhou, Tong" sort="Zhou, Tong" uniqKey="Zhou T" first="Tong" last="Zhou">Tong Zhou</name>
</country>
</tree>
</affiliations>
</record>
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