Please use this identifier to cite or link to this item:
https://doi.org/10.1089/ars.2019.7850
DC Field | Value | |
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dc.title | Cysteine Deprivation Targets Ovarian Clear Cell Carcinoma Via Oxidative Stress and Iron-Sulfur Cluster Biogenesis Deficit | |
dc.contributor.author | WISNA NOVERA | |
dc.contributor.author | LEE ZHENG WEI | |
dc.contributor.author | NIN SIJIN,DAWN | |
dc.contributor.author | Dai, MZY | |
dc.contributor.author | SHABANA BINTE IDRES | |
dc.contributor.author | Wu, H | |
dc.contributor.author | Damen, JMA | |
dc.contributor.author | Tan Tuan Zea | |
dc.contributor.author | SIM YI LOONG, ARTHUR | |
dc.contributor.author | LONG YUN CHAU | |
dc.contributor.author | Wu, W | |
dc.contributor.author | HUANG YUN JU,RUBY | |
dc.contributor.author | DENG LIH WEN | |
dc.date.accessioned | 2021-03-22T06:35:42Z | |
dc.date.available | 2021-03-22T06:35:42Z | |
dc.date.issued | 2020-12-10 | |
dc.identifier.citation | WISNA NOVERA, LEE ZHENG WEI, NIN SIJIN,DAWN, Dai, MZY, SHABANA BINTE IDRES, Wu, H, Damen, JMA, Tan Tuan Zea, SIM YI LOONG, ARTHUR, LONG YUN CHAU, Wu, W, HUANG YUN JU,RUBY, DENG LIH WEN (2020-12-10). Cysteine Deprivation Targets Ovarian Clear Cell Carcinoma Via Oxidative Stress and Iron-Sulfur Cluster Biogenesis Deficit. Antioxidants and Redox Signaling 33 (17) : 1191-1208. ScholarBank@NUS Repository. https://doi.org/10.1089/ars.2019.7850 | |
dc.identifier.issn | 1523-0864 | |
dc.identifier.issn | 1557-7716 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/187460 | |
dc.description.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. | |
dc.publisher | Mary Ann Liebert Inc | |
dc.source | Elements | |
dc.subject | cystathionase | |
dc.subject | cysteine | |
dc.subject | iron−sulfur cluster | |
dc.subject | mitochondria | |
dc.subject | oxidative stress | |
dc.subject | system xc− | |
dc.type | Article | |
dc.date.updated | 2021-03-22T05:06:57Z | |
dc.contributor.department | ANATOMY | |
dc.contributor.department | BIOCHEMISTRY | |
dc.contributor.department | OBSTETRICS & GYNAECOLOGY | |
dc.description.doi | 10.1089/ars.2019.7850 | |
dc.description.sourcetitle | Antioxidants and Redox Signaling | |
dc.description.volume | 33 | |
dc.description.issue | 17 | |
dc.description.page | 1191-1208 | |
dc.published.state | Published | |
Appears in Collections: | Staff Publications Elements |
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