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Article: Mediating K+/H+ Transport on Organelle Membranes to Selectively Eradicate Cancer Stem Cells with a Small Molecule

TitleMediating K+/H+ Transport on Organelle Membranes to Selectively Eradicate Cancer Stem Cells with a Small Molecule
Authors
Issue Date2020
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jacsat/index.html
Citation
Journal of the American Chemical Society, 2020, v. 142, p. 10769-10779 How to Cite?
AbstractMolecules that are capable of disrupting cellular ion homeostasis offer unique opportunities to treat cancer. However, previously reported synthetic ion transporters showed limited value, as promiscuous ionic disruption caused toxicity to both healthy cells and cancer cells indiscriminately. Here we report a simple yet efficient synthetic K+ transporter that takes advantage of the endogenous subcellular pH gradient and membrane potential to site-selectively mediate K+/H+ transport on the mitochondrial and lysosomal membranes in living cells. Consequent mitochondrial and lysosomal damages enhanced cytotoxicity to chemo-resistant ovarian cancer stem cells (CSCs) via apoptosis induction and autophagy suppression with remarkable selectivity (up to 47-fold). The eradication of CSCs blunted tumor formation in mice. We believe this strategy can be exploited in the structural design and applications of next-generation synthetic cation transporters for the treatment of cancer and other diseases related to dysfunctional K+ channels.
Persistent Identifierhttp://hdl.handle.net/10722/293265
ISSN
2020 Impact Factor: 15.419
2020 SCImago Journal Rankings: 7.115
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSHEN, FF-
dc.contributor.authorDAI, SY-
dc.contributor.authorWONG, NK-
dc.contributor.authorDeng, S-
dc.contributor.authorWong, AST-
dc.contributor.authorYang, D-
dc.date.accessioned2020-11-23T08:14:14Z-
dc.date.available2020-11-23T08:14:14Z-
dc.date.issued2020-
dc.identifier.citationJournal of the American Chemical Society, 2020, v. 142, p. 10769-10779-
dc.identifier.issn0002-7863-
dc.identifier.urihttp://hdl.handle.net/10722/293265-
dc.description.abstractMolecules that are capable of disrupting cellular ion homeostasis offer unique opportunities to treat cancer. However, previously reported synthetic ion transporters showed limited value, as promiscuous ionic disruption caused toxicity to both healthy cells and cancer cells indiscriminately. Here we report a simple yet efficient synthetic K+ transporter that takes advantage of the endogenous subcellular pH gradient and membrane potential to site-selectively mediate K+/H+ transport on the mitochondrial and lysosomal membranes in living cells. Consequent mitochondrial and lysosomal damages enhanced cytotoxicity to chemo-resistant ovarian cancer stem cells (CSCs) via apoptosis induction and autophagy suppression with remarkable selectivity (up to 47-fold). The eradication of CSCs blunted tumor formation in mice. We believe this strategy can be exploited in the structural design and applications of next-generation synthetic cation transporters for the treatment of cancer and other diseases related to dysfunctional K+ channels.-
dc.languageeng-
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jacsat/index.html-
dc.relation.ispartofJournal of the American Chemical Society-
dc.rightsThis document is the Accepted Manuscript version of a Published Work that appeared in final form in [JournalTitle], copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see [insert ACS Articles on Request author-directed link to Published Work, see http://pubs.acs.org/page/policy/articlesonrequest/index.html].-
dc.titleMediating K+/H+ Transport on Organelle Membranes to Selectively Eradicate Cancer Stem Cells with a Small Molecule-
dc.typeArticle-
dc.identifier.emailDeng, S: dengshan@hku.hk-
dc.identifier.emailWong, AST: awong1@hku.hk-
dc.identifier.emailYang, D: yangdan@hku.hk-
dc.identifier.authorityWong, AST=rp00805-
dc.identifier.authorityYang, D=rp00825-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1021/jacs.0c02134-
dc.identifier.pmid32441923-
dc.identifier.scopuseid_2-s2.0-85086619606-
dc.identifier.hkuros319219-
dc.identifier.volume142-
dc.identifier.spage10769-
dc.identifier.epage10779-
dc.identifier.isiWOS:000542929600022-
dc.publisher.placeUnited States-
dc.identifier.issnl0002-7863-

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