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Lysosomal Destabilizing Drug Siramesine and the Dual Tyrosine Kinase Inhibitor Lapatinib Induce a Synergistic Ferroptosis through Reduced Heme Oxygenase-1 (HO-1) Levels
المؤلفون المشاركون
Gibson, Spencer
Villalpando-Rodriguez, Gloria E.
Blankstein, Anna R.
Konzelman, Carmen
المصدر
Oxidative Medicine and Cellular Longevity
العدد
المجلد 2019، العدد 2019 (31 ديسمبر/كانون الأول 2019)، ص ص. 1-14، 14ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2019-09-17
دولة النشر
مصر
عدد الصفحات
14
التخصصات الرئيسية
الملخص EN
Ferroptosis is an iron-dependent type of cell death distinct from apoptosis or necrosis characterized by accumulation of reactive oxygen species.
The combination of siramesine, a lysosomotropic agent, and lapatinib, a dual tyrosine kinase inhibitor (TKI), synergistically induced cell death in breast cancer cells mediated by ferroptosis.
In this study, we showed that this combination of siramesine and lapatinib induces synergistic cell death in glioma cell line U87 and lung adenocarcinoma cell line A549.
This cell death was characterized by the increase in iron content, reactive oxygen species (ROS) production, and lipid peroxidation accumulation after 24 hours of treatment.
Moreover, iron chelator DFO and ferrostatin-1, a ferroptosis inhibitor, significantly reduced cell death.
The mechanism underlying the activation of the ferroptotic pathway involves lysosomal permeabilization and increase in reactive iron levels in these cells.
In addition, the downregulation of heme oxygenase-1 (HO-1) protein occurred.
Overexpression of HO-1 resulted in reduction of ROS and lipid peroxidation production and cell death.
Furthermore, knocking down of HO-1 combined with siramesine treatment resulted in increased cell death.
Finally, we found that the inhibition of the proteasome system rescued HO-1 expression levels.
Our results suggest that the induction of ferroptosis by combining a lysosomotropic agent and a tyrosine kinase inhibitor is mediated by iron release from lysosomes and HO-1 degradation by the proteasome system.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Villalpando-Rodriguez, Gloria E.& Blankstein, Anna R.& Konzelman, Carmen& Gibson, Spencer. 2019. Lysosomal Destabilizing Drug Siramesine and the Dual Tyrosine Kinase Inhibitor Lapatinib Induce a Synergistic Ferroptosis through Reduced Heme Oxygenase-1 (HO-1) Levels. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1206474
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Villalpando-Rodriguez, Gloria E.…[et al.]. Lysosomal Destabilizing Drug Siramesine and the Dual Tyrosine Kinase Inhibitor Lapatinib Induce a Synergistic Ferroptosis through Reduced Heme Oxygenase-1 (HO-1) Levels. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-14.
https://search.emarefa.net/detail/BIM-1206474
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Villalpando-Rodriguez, Gloria E.& Blankstein, Anna R.& Konzelman, Carmen& Gibson, Spencer. Lysosomal Destabilizing Drug Siramesine and the Dual Tyrosine Kinase Inhibitor Lapatinib Induce a Synergistic Ferroptosis through Reduced Heme Oxygenase-1 (HO-1) Levels. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1206474
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1206474
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
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