Cellular Mechanisms Triggered by the Cotreatment of Resveratrol and Doxorubicin in Breast Cancer: A Translational In Vitro–In Silico Model
المؤلفون المشاركون
Vargas, José Eduardo
Puga, Renato
Lenz, Guido
Trindade, Cristiano
Filippi-Chiela, Eduardo
المصدر
Oxidative Medicine and Cellular Longevity
العدد
المجلد 2020، العدد 2020 (31 ديسمبر/كانون الأول 2020)، ص ص. 1-23، 23ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2020-11-02
دولة النشر
مصر
عدد الصفحات
23
التخصصات الرئيسية
الملخص EN
Doxorubicin (Doxo) is the most effective chemotherapeutic agent for the treatment of breast cancer.
However, resistance to Doxo is common.
Adjuvant compounds capable of modulating mechanisms involved in Doxo resistance may potentiate the effectiveness of the drug.
Resveratrol (Rsv) has been tested as an adjuvant in mammary malignancies.
However, the cellular and molecular mechanisms underlying the effects of cotreatment with Doxo and Rsv in breast cancer are poorly understood.
Here, we combined in vitro and in silico analysis to characterize these mechanisms.
In vitro, we employed a clinically relevant experimental design consisting of acute (24 h) treatment followed by 15 days of analysis.
Acute Rsv potentiated the long-lasting effect of Doxo through the induction of apoptosis and senescence.
Cells that survived to the cotreatment triggered high levels of autophagy.
Autophagy inhibition during its peak of activation but not concomitant with Doxo+Rsv increased the long-term toxicity of the cotreatment.
To uncover key proteins potentially associated with in vitro effects, an in silico multistep strategy was implemented.
Chemical-protein networks were predicted based on constitutive gene expression of MCF7 cells and interatomic data from breast cancer.
Topological analysis, KM survival analysis, and a quantitative model based on the connectivity between apoptosis, senescence, and autophagy were performed.
We found seven putative genes predicted to be modulated by Rsv in the context of Doxo treatment: CCND1, CDH1, ESR1, HSP90AA1, MAPK3, PTPN11, and RPS6KB1.
Six out of these seven genes have been experimentally proven to be modulated by Rsv in cancer cells, with 4 of the 6 genes in MCF7 cells.
In conclusion, acute Rsv potentiated the long-term toxicity of Doxo in breast cancer potentially through the modulation of genes and mechanisms involved in Doxo resistance.
Rational autophagy inhibition potentiated the effects of Rsv+Doxo, a strategy that should be further tested in animal models.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Vargas, José Eduardo& Puga, Renato& Lenz, Guido& Trindade, Cristiano& Filippi-Chiela, Eduardo. 2020. Cellular Mechanisms Triggered by the Cotreatment of Resveratrol and Doxorubicin in Breast Cancer: A Translational In Vitro–In Silico Model. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-23.
https://search.emarefa.net/detail/BIM-1204860
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Vargas, José Eduardo…[et al.]. Cellular Mechanisms Triggered by the Cotreatment of Resveratrol and Doxorubicin in Breast Cancer: A Translational In Vitro–In Silico Model. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-23.
https://search.emarefa.net/detail/BIM-1204860
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Vargas, José Eduardo& Puga, Renato& Lenz, Guido& Trindade, Cristiano& Filippi-Chiela, Eduardo. Cellular Mechanisms Triggered by the Cotreatment of Resveratrol and Doxorubicin in Breast Cancer: A Translational In Vitro–In Silico Model. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-23.
https://search.emarefa.net/detail/BIM-1204860
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1204860
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر