Cysteine Deprivation Targets Ovarian Clear Cell Carcinoma Via Oxidative Stress and Iron-Sulfur Cluster Biogenesis Deficit.
Identifieur interne : 000149 ( Main/Exploration ); précédent : 000148; suivant : 000150Cysteine Deprivation Targets Ovarian Clear Cell Carcinoma Via Oxidative Stress and Iron-Sulfur Cluster Biogenesis Deficit.
Auteurs : Wisna Novera [Singapour] ; Zheng-Wei Lee [Singapour] ; Dawn Sijin Nin [Singapour] ; Melvin Zi-Yu Dai [Singapour] ; Shabana Binte Idres [Singapour] ; Hui Wu [Singapour] ; J Mirjam A. Damen [Pays-Bas] ; Tuan Zea Tan [Singapour] ; Arthur Yi Loong Sim [Singapour] ; Yun Chau Long [Singapour] ; Wei Wu [Pays-Bas] ; Ruby Yun-Ju Huang [Singapour] ; Lih-Wen Deng [Singapour]Source :
- Antioxidants & redox signaling [ 1557-7716 ] ; 2020.
Abstract
Aims: Current treatment options for ovarian clear cell carcinoma (OCCC) are limited to combination of platinum-based and other cytotoxic agents to which patients respond poorly due to intrinsic chemoresistance. There is therefore an urgent need to develop alternative therapeutic strategies for OCCC. Results: Cysteine deprivation suppresses OCCC growth in vitro and in vivo with no apparent toxicity. Modes of cell death induced by cysteine deprivation in OCCC are determined by their innate metabolic profiles. Cysteine-deprived glycolytic OCCC is abolished primarily by oxidative stress-dependent necrosis and ferroptosis, which can otherwise be prevented by pretreatment with antioxidative agents. Meanwhile, OCCC that relies on mitochondria respiration for its bioenergetics is suppressed through apoptosis, which can otherwise be averted by pretreatment with cysteine precursor alone, but not with antioxidative agents. Cysteine deprivation induces apoptosis in respiring OCCC by limiting iron-sulfur (Fe-S) cluster synthesis in the mitochondria, without which electron transport chain may be disrupted. Respiring OCCC responds to Fe-S cluster deficit by increasing iron influx into the mitochondria, which leads to iron overload, mitochondria damage, and eventual cell death. Innovation/Conclusion: This study demonstrates the importance of cysteine availability in OCCC that is for its antioxidative property and its less appreciated role in mitochondria respiration. Regardless of OCCC metabolic profiles, cysteine deprivation abolishes both glycolytic and respiring OCCC growth in vitro and in vivo. Conclusion: This study highlights the therapeutic potential of cysteine deprivation for OCCC.
DOI: 10.1089/ars.2019.7850
PubMed: 32336105
Affiliations:
- Pays-Bas, Singapour
- Utrecht (province)
- Utrecht
- Université d'Utrecht, Université nationale de Singapour
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cysteine Deprivation Targets Ovarian Clear Cell Carcinoma <i>Via</i> Oxidative Stress and Iron-Sulfur Cluster Biogenesis Deficit.</title><author><name sortKey="Novera, Wisna" sort="Novera, Wisna" uniqKey="Novera W" first="Wisna" last="Novera">Wisna Novera</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Lee, Zheng Wei" sort="Lee, Zheng Wei" uniqKey="Lee Z" first="Zheng-Wei" last="Lee">Zheng-Wei Lee</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Nin, Dawn Sijin" sort="Nin, Dawn Sijin" uniqKey="Nin D" first="Dawn Sijin" last="Nin">Dawn Sijin Nin</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Dai, Melvin Zi Yu" sort="Dai, Melvin Zi Yu" uniqKey="Dai M" first="Melvin Zi-Yu" last="Dai">Melvin Zi-Yu Dai</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Binte Idres, Shabana" sort="Binte Idres, Shabana" uniqKey="Binte Idres S" first="Shabana" last="Binte Idres">Shabana Binte Idres</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Wu, Hui" sort="Wu, Hui" uniqKey="Wu H" first="Hui" last="Wu">Hui Wu</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Damen, J Mirjam A" sort="Damen, J Mirjam A" uniqKey="Damen J" first="J Mirjam A" last="Damen">J Mirjam A. Damen</name><affiliation wicri:level="4"><nlm:affiliation>Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Tan, Tuan Zea" sort="Tan, Tuan Zea" uniqKey="Tan T" first="Tuan Zea" last="Tan">Tuan Zea Tan</name><affiliation wicri:level="4"><nlm:affiliation>Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Cancer Science Institute of Singapore, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Sim, Arthur Yi Loong" sort="Sim, Arthur Yi Loong" uniqKey="Sim A" first="Arthur Yi Loong" last="Sim">Arthur Yi Loong Sim</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Long, Yun Chau" sort="Long, Yun Chau" uniqKey="Long Y" first="Yun Chau" last="Long">Yun Chau Long</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Wu, Wei" sort="Wu, Wei" uniqKey="Wu W" first="Wei" last="Wu">Wei Wu</name><affiliation wicri:level="4"><nlm:affiliation>Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Huang, Ruby Yun Ju" sort="Huang, Ruby Yun Ju" uniqKey="Huang R" first="Ruby Yun-Ju" last="Huang">Ruby Yun-Ju Huang</name><affiliation wicri:level="4"><nlm:affiliation>Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Cancer Science Institute of Singapore, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Obstetrics and Gynaecology, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Obstetrics and Gynaecology, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Deng, Lih Wen" sort="Deng, Lih Wen" uniqKey="Deng L" first="Lih-Wen" last="Deng">Lih-Wen Deng</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation><affiliation wicri:level="1"><nlm:affiliation>National University Cancer Institute, National University Health System, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>National University Cancer Institute, National University Health System, Singapore</wicri:regionArea><wicri:noRegion>Singapore</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32336105</idno><idno type="pmid">32336105</idno><idno type="doi">10.1089/ars.2019.7850</idno><idno type="wicri:Area/Main/Corpus">000103</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000103</idno><idno type="wicri:Area/Main/Curation">000103</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000103</idno><idno type="wicri:Area/Main/Exploration">000103</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Cysteine Deprivation Targets Ovarian Clear Cell Carcinoma <i>Via</i> Oxidative Stress and Iron-Sulfur Cluster Biogenesis Deficit.</title><author><name sortKey="Novera, Wisna" sort="Novera, Wisna" uniqKey="Novera W" first="Wisna" last="Novera">Wisna Novera</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Lee, Zheng Wei" sort="Lee, Zheng Wei" uniqKey="Lee Z" first="Zheng-Wei" last="Lee">Zheng-Wei Lee</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Nin, Dawn Sijin" sort="Nin, Dawn Sijin" uniqKey="Nin D" first="Dawn Sijin" last="Nin">Dawn Sijin Nin</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Dai, Melvin Zi Yu" sort="Dai, Melvin Zi Yu" uniqKey="Dai M" first="Melvin Zi-Yu" last="Dai">Melvin Zi-Yu Dai</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Binte Idres, Shabana" sort="Binte Idres, Shabana" uniqKey="Binte Idres S" first="Shabana" last="Binte Idres">Shabana Binte Idres</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Wu, Hui" sort="Wu, Hui" uniqKey="Wu H" first="Hui" last="Wu">Hui Wu</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Damen, J Mirjam A" sort="Damen, J Mirjam A" uniqKey="Damen J" first="J Mirjam A" last="Damen">J Mirjam A. Damen</name><affiliation wicri:level="4"><nlm:affiliation>Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Tan, Tuan Zea" sort="Tan, Tuan Zea" uniqKey="Tan T" first="Tuan Zea" last="Tan">Tuan Zea Tan</name><affiliation wicri:level="4"><nlm:affiliation>Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Cancer Science Institute of Singapore, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Sim, Arthur Yi Loong" sort="Sim, Arthur Yi Loong" uniqKey="Sim A" first="Arthur Yi Loong" last="Sim">Arthur Yi Loong Sim</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Long, Yun Chau" sort="Long, Yun Chau" uniqKey="Long Y" first="Yun Chau" last="Long">Yun Chau Long</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Wu, Wei" sort="Wu, Wei" uniqKey="Wu W" first="Wei" last="Wu">Wei Wu</name><affiliation wicri:level="4"><nlm:affiliation>Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Huang, Ruby Yun Ju" sort="Huang, Ruby Yun Ju" uniqKey="Huang R" first="Ruby Yun-Ju" last="Huang">Ruby Yun-Ju Huang</name><affiliation wicri:level="4"><nlm:affiliation>Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Cancer Science Institute of Singapore, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Obstetrics and Gynaecology, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Obstetrics and Gynaecology, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Deng, Lih Wen" sort="Deng, Lih Wen" uniqKey="Deng L" first="Lih-Wen" last="Deng">Lih-Wen Deng</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation><affiliation wicri:level="1"><nlm:affiliation>National University Cancer Institute, National University Health System, Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>National University Cancer Institute, National University Health System, Singapore</wicri:regionArea><wicri:noRegion>Singapore</wicri:noRegion></affiliation></author></analytic><series><title level="j">Antioxidants & redox signaling</title><idno type="eISSN">1557-7716</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><b><i>Aims:</i></b> Current treatment options for ovarian clear cell carcinoma (OCCC) are limited to combination of platinum-based and other cytotoxic agents to which patients respond poorly due to intrinsic chemoresistance. There is therefore an urgent need to develop alternative therapeutic strategies for OCCC. <b><i>Results:</i></b> Cysteine deprivation suppresses OCCC growth <i>in vitro</i> and <i>in vivo</i> with no apparent toxicity. Modes of cell death induced by cysteine deprivation in OCCC are determined by their innate metabolic profiles. Cysteine-deprived glycolytic OCCC is abolished primarily by oxidative stress-dependent necrosis and ferroptosis, which can otherwise be prevented by pretreatment with antioxidative agents. Meanwhile, OCCC that relies on mitochondria respiration for its bioenergetics is suppressed through apoptosis, which can otherwise be averted by pretreatment with cysteine precursor alone, but not with antioxidative agents. Cysteine deprivation induces apoptosis in respiring OCCC by limiting iron-sulfur (Fe-S) cluster synthesis in the mitochondria, without which electron transport chain may be disrupted. Respiring OCCC responds to Fe-S cluster deficit by increasing iron influx into the mitochondria, which leads to iron overload, mitochondria damage, and eventual cell death. <b><i>Innovation/Conclusion:</i></b> This study demonstrates the importance of cysteine availability in OCCC that is for its antioxidative property and its less appreciated role in mitochondria respiration. Regardless of OCCC metabolic profiles, cysteine deprivation abolishes both glycolytic and respiring OCCC growth <i>in vitro</i> and <i>in vivo</i>. <b><i>Conclusion:</i></b> This study highlights the therapeutic potential of cysteine deprivation for OCCC.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">32336105</PMID><DateRevised><Year>2020</Year><Month>11</Month><Day>10</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1557-7716</ISSN><JournalIssue CitedMedium="Internet"><Volume>33</Volume><Issue>17</Issue><PubDate><Year>2020</Year><Month>Dec</Month><Day>10</Day></PubDate></JournalIssue><Title>Antioxidants & redox signaling</Title><ISOAbbreviation>Antioxid Redox Signal</ISOAbbreviation></Journal><ArticleTitle>Cysteine Deprivation Targets Ovarian Clear Cell Carcinoma <i>Via</i> Oxidative Stress and Iron-Sulfur Cluster Biogenesis Deficit.</ArticleTitle><Pagination><MedlinePgn>1191-1208</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1089/ars.2019.7850</ELocationID><Abstract><AbstractText><b><i>Aims:</i></b> Current treatment options for ovarian clear cell carcinoma (OCCC) are limited to combination of platinum-based and other cytotoxic agents to which patients respond poorly due to intrinsic chemoresistance. There is therefore an urgent need to develop alternative therapeutic strategies for OCCC. <b><i>Results:</i></b> Cysteine deprivation suppresses OCCC growth <i>in vitro</i> and <i>in vivo</i> with no apparent toxicity. Modes of cell death induced by cysteine deprivation in OCCC are determined by their innate metabolic profiles. Cysteine-deprived glycolytic OCCC is abolished primarily by oxidative stress-dependent necrosis and ferroptosis, which can otherwise be prevented by pretreatment with antioxidative agents. Meanwhile, OCCC that relies on mitochondria respiration for its bioenergetics is suppressed through apoptosis, which can otherwise be averted by pretreatment with cysteine precursor alone, but not with antioxidative agents. Cysteine deprivation induces apoptosis in respiring OCCC by limiting iron-sulfur (Fe-S) cluster synthesis in the mitochondria, without which electron transport chain may be disrupted. Respiring OCCC responds to Fe-S cluster deficit by increasing iron influx into the mitochondria, which leads to iron overload, mitochondria damage, and eventual cell death. <b><i>Innovation/Conclusion:</i></b> This study demonstrates the importance of cysteine availability in OCCC that is for its antioxidative property and its less appreciated role in mitochondria respiration. Regardless of OCCC metabolic profiles, cysteine deprivation abolishes both glycolytic and respiring OCCC growth <i>in vitro</i> and <i>in vivo</i>. <b><i>Conclusion:</i></b> This study highlights the therapeutic potential of cysteine deprivation for OCCC.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Novera</LastName><ForeName>Wisna</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Zheng-Wei</ForeName><Initials>ZW</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nin</LastName><ForeName>Dawn Sijin</ForeName><Initials>DS</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dai</LastName><ForeName>Melvin Zi-Yu</ForeName><Initials>MZ</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Binte Idres</LastName><ForeName>Shabana</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Hui</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Damen</LastName><ForeName>J Mirjam A</ForeName><Initials>JMA</Initials><AffiliationInfo><Affiliation>Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Tuan Zea</ForeName><Initials>TZ</Initials><AffiliationInfo><Affiliation>Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sim</LastName><ForeName>Arthur Yi Loong</ForeName><Initials>AYL</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Long</LastName><ForeName>Yun Chau</ForeName><Initials>YC</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Wei</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Ruby Yun-Ju</ForeName><Initials>RY</Initials><AffiliationInfo><Affiliation>Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Obstetrics and Gynaecology, National University of Singapore, Singapore, Singapore.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Deng</LastName><ForeName>Lih-Wen</ForeName><Initials>LW</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>National University Cancer Institute, National University Health System, Singapore, Singapore.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>05</Month><Day>19</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Antioxid Redox Signal</MedlineTA><NlmUniqueID>100888899</NlmUniqueID><ISSNLinking>1523-0864</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">cystathionase</Keyword><Keyword MajorTopicYN="N">cysteine</Keyword><Keyword MajorTopicYN="N">iron−sulfur cluster</Keyword><Keyword MajorTopicYN="N">mitochondria</Keyword><Keyword MajorTopicYN="N">oxidative stress</Keyword><Keyword MajorTopicYN="N">system xc−</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>4</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>4</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>4</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32336105</ArticleId><ArticleId IdType="doi">10.1089/ars.2019.7850</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Pays-Bas</li><li>Singapour</li></country><region><li>Utrecht (province)</li></region><settlement><li>Utrecht</li></settlement><orgName><li>Université d'Utrecht</li><li>Université nationale de Singapour</li></orgName></list><tree><country name="Singapour"><noRegion><name sortKey="Novera, Wisna" sort="Novera, Wisna" uniqKey="Novera W" first="Wisna" last="Novera">Wisna Novera</name></noRegion><name sortKey="Binte Idres, Shabana" sort="Binte Idres, Shabana" uniqKey="Binte Idres S" first="Shabana" last="Binte Idres">Shabana Binte Idres</name><name sortKey="Dai, Melvin Zi Yu" sort="Dai, Melvin Zi Yu" uniqKey="Dai M" first="Melvin Zi-Yu" last="Dai">Melvin Zi-Yu Dai</name><name sortKey="Deng, Lih Wen" sort="Deng, Lih Wen" uniqKey="Deng L" first="Lih-Wen" last="Deng">Lih-Wen Deng</name><name sortKey="Deng, Lih Wen" sort="Deng, Lih Wen" uniqKey="Deng L" first="Lih-Wen" last="Deng">Lih-Wen Deng</name><name sortKey="Huang, Ruby Yun Ju" sort="Huang, Ruby Yun Ju" uniqKey="Huang R" first="Ruby Yun-Ju" last="Huang">Ruby Yun-Ju Huang</name><name sortKey="Huang, Ruby Yun Ju" sort="Huang, Ruby Yun Ju" uniqKey="Huang R" first="Ruby Yun-Ju" last="Huang">Ruby Yun-Ju Huang</name><name sortKey="Huang, Ruby Yun Ju" sort="Huang, Ruby Yun Ju" uniqKey="Huang R" first="Ruby Yun-Ju" last="Huang">Ruby Yun-Ju Huang</name><name sortKey="Lee, Zheng Wei" sort="Lee, Zheng Wei" uniqKey="Lee Z" first="Zheng-Wei" last="Lee">Zheng-Wei Lee</name><name sortKey="Long, Yun Chau" sort="Long, Yun Chau" uniqKey="Long Y" first="Yun Chau" last="Long">Yun Chau Long</name><name sortKey="Nin, Dawn Sijin" sort="Nin, Dawn Sijin" uniqKey="Nin D" first="Dawn Sijin" last="Nin">Dawn Sijin Nin</name><name sortKey="Sim, Arthur Yi Loong" sort="Sim, Arthur Yi Loong" uniqKey="Sim A" first="Arthur Yi Loong" last="Sim">Arthur Yi Loong Sim</name><name sortKey="Tan, Tuan Zea" sort="Tan, Tuan Zea" uniqKey="Tan T" first="Tuan Zea" last="Tan">Tuan Zea Tan</name><name sortKey="Wu, Hui" sort="Wu, Hui" uniqKey="Wu H" first="Hui" last="Wu">Hui Wu</name></country><country name="Pays-Bas"><region name="Utrecht (province)"><name sortKey="Damen, J Mirjam A" sort="Damen, J Mirjam A" uniqKey="Damen J" first="J Mirjam A" last="Damen">J Mirjam A. Damen</name></region><name sortKey="Wu, Wei" sort="Wu, Wei" uniqKey="Wu W" first="Wei" last="Wu">Wei Wu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Bois/explor/IronSulferCluV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000149 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000149 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Bois
|area= IronSulferCluV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:32336105
|texte= Cysteine Deprivation Targets Ovarian Clear Cell Carcinoma Via Oxidative Stress and Iron-Sulfur Cluster Biogenesis Deficit.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:32336105" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a IronSulferCluV1
| This area was generated with Dilib version V0.6.38. |  |