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- Publisher Website: 10.1021/jacs.0c02134
- Scopus: eid_2-s2.0-85086619606
- PMID: 32441923
- WOS: WOS:000542929600022
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Article: Mediating K+/H+ Transport on Organelle Membranes to Selectively Eradicate Cancer Stem Cells with a Small Molecule
Title | Mediating K+/H+ Transport on Organelle Membranes to Selectively Eradicate Cancer Stem Cells with a Small Molecule |
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Authors | |
Issue Date | 2020 |
Publisher | American 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? |
Abstract | Molecules 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 Identifier | http://hdl.handle.net/10722/293265 |
ISSN | 2023 Impact Factor: 14.4 2023 SCImago Journal Rankings: 5.489 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | SHEN, FF | - |
dc.contributor.author | DAI, SY | - |
dc.contributor.author | WONG, NK | - |
dc.contributor.author | Deng, S | - |
dc.contributor.author | Wong, AST | - |
dc.contributor.author | Yang, D | - |
dc.date.accessioned | 2020-11-23T08:14:14Z | - |
dc.date.available | 2020-11-23T08:14:14Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Journal of the American Chemical Society, 2020, v. 142, p. 10769-10779 | - |
dc.identifier.issn | 0002-7863 | - |
dc.identifier.uri | http://hdl.handle.net/10722/293265 | - |
dc.description.abstract | Molecules 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.language | eng | - |
dc.publisher | American Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jacsat/index.html | - |
dc.relation.ispartof | Journal of the American Chemical Society | - |
dc.rights | This 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.title | Mediating K+/H+ Transport on Organelle Membranes to Selectively Eradicate Cancer Stem Cells with a Small Molecule | - |
dc.type | Article | - |
dc.identifier.email | Deng, S: dengshan@hku.hk | - |
dc.identifier.email | Wong, AST: awong1@hku.hk | - |
dc.identifier.email | Yang, D: yangdan@hku.hk | - |
dc.identifier.authority | Wong, AST=rp00805 | - |
dc.identifier.authority | Yang, D=rp00825 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1021/jacs.0c02134 | - |
dc.identifier.pmid | 32441923 | - |
dc.identifier.scopus | eid_2-s2.0-85086619606 | - |
dc.identifier.hkuros | 319219 | - |
dc.identifier.volume | 142 | - |
dc.identifier.spage | 10769 | - |
dc.identifier.epage | 10779 | - |
dc.identifier.isi | WOS:000542929600022 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 0002-7863 | - |