Proscillaridin A Promotes Oxidative Stress and ER Stress, Inhibits STAT3 Activation, and Induces Apoptosis in A549 Lung Adenocarcinoma Cells
المؤلفون المشاركون
Khan, Muhammad
Ma, Tonghui
Maryam, Amara
Mehmood, Tahir
Yan, Qiulong
Li, Yongming
المصدر
Oxidative Medicine and Cellular Longevity
العدد
المجلد 2018، العدد 2018 (31 ديسمبر/كانون الأول 2018)، ص ص. 1-17، 17ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2018-01-11
دولة النشر
مصر
عدد الصفحات
17
التخصصات الرئيسية
الملخص EN
Cardiac glycosides are natural compounds used for the treatment of cardiovascular disorders.
Although originally prescribed for cardiovascular diseases, more recently, they have been rediscovered for their potential use in the treatment of cancer.
Proscillaridin A (PSD-A), a cardiac glycoside component of Urginea maritima, has been reported to exhibit anticancer activity.
However, the cellular targets and anticancer mechanism of PSD-A in various cancers including lung cancer remain largely unexplored.
In the present study, we found that PSD-A inhibits growth and induces apoptosis in A549 lung adenocarcinoma cells.
The anticancer activity of PSD-A was found to be associated with the activation of JNK, induction of ER stress, mitochondrial dysfunction, and inhibition of STAT3 activation.
PSD-A induces oxidative stress as evidenced from ROS generation, GSH depletion, and decreased activity of TrxR1.
PSD-A-mediated ER stress was verified by increased phosphorylation of eIF2α and expression of its downstream effector proteins ATF4, CHOP, and caspases-4.
PSD-A triggered apoptosis by inducing JNK (1/2) activation, increasing bax/bcl-2 ratio, dissipating mitochondrial membrane potential, and inducing cleavage of caspases and PARP.
Further study revealed that PSD-A inhibits both constitutive and inducible STAT3 activations and decreases STAT3 DNA-binding activity.
Moreover, PSD-A-mediated inhibition of STAT3 activation was found to be associated with increased SHP-1 expression, decreased phosphorylation of Src, and binding of PSD-A with STAT3 SH2 domain.
Finally, STAT3 knockdown by shRNA inhibited growth and enhanced apoptotic efficacy of PSD-A.
Taken together, the data suggest that PSD-A could be developed into a potential therapeutic agent against lung adenocarcinoma.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Maryam, Amara& Mehmood, Tahir& Yan, Qiulong& Li, Yongming& Khan, Muhammad& Ma, Tonghui. 2018. Proscillaridin A Promotes Oxidative Stress and ER Stress, Inhibits STAT3 Activation, and Induces Apoptosis in A549 Lung Adenocarcinoma Cells. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-17.
https://search.emarefa.net/detail/BIM-1211318
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Maryam, Amara…[et al.]. Proscillaridin A Promotes Oxidative Stress and ER Stress, Inhibits STAT3 Activation, and Induces Apoptosis in A549 Lung Adenocarcinoma Cells. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-17.
https://search.emarefa.net/detail/BIM-1211318
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Maryam, Amara& Mehmood, Tahir& Yan, Qiulong& Li, Yongming& Khan, Muhammad& Ma, Tonghui. Proscillaridin A Promotes Oxidative Stress and ER Stress, Inhibits STAT3 Activation, and Induces Apoptosis in A549 Lung Adenocarcinoma Cells. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-17.
https://search.emarefa.net/detail/BIM-1211318
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1211318
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