دورية أكاديمية
Exploiting ROS and metabolic differences to kill cisplatin resistant lung cancer
| العنوان: | Exploiting ROS and metabolic differences to kill cisplatin resistant lung cancer |
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| المساهمون: | Kandemir, Hande, Wangpaichitr, M., Wu, C. J., Li, Y. Y., Nguyen, D. J. M., Shah, S., Chen, S. M., Feun, L. G., Prince, J. S., Kuo, M. T., Savaraj, N., School of Medicine, Department of Internal Medicine |
| المصدر: | Oncotarget |
| بيانات النشر: | Impact Journals International |
| سنة النشر: | 2017 |
| المجموعة: | Koç University Suna Kıraç Library’ Digital Collections |
| مصطلحات موضوعية: | Internal medicine, Glutamate release inhibitor, X(C)(-) cystine/glutamate antiporter, Amyotrophic-lateral-sclerosis, Lactate-dehydrogenase, Riluzole, Cells, Growth, Proliferation, Sensitivity, Melanoma |
| الوصف: | Cisplatin resistance remains a major problem in the treatment of lung cancer. We have discovered that cisplatin resistant (CR) lung cancer cells, regardless of the signaling pathway status, share the common parameter which is an increase in reactive oxygen species (ROS) and undergo metabolic reprogramming. CR cells were no longer addicted to the glycolytic pathway, but rather relied on oxidative metabolism. They took up twice as much glutamine and were highly sensitive to glutamine deprivation. Glutamine is hydrolyzed to glutamate for glutathione synthesis, an essential factor to abrogate high ROS via xCT antiporter. Thus, blocking glutamate flux using riluzole (an amyotropic lateral sclerosis approved drug) can selectively kill CR cells in vitro and in vivo. However, we discovered here that glutathione suppression is not the primary pathway in eradicating the CR cells. Riluzole can lead to further decrease in NAD(+) (nicotinamide adenine dinucleotide) and lactate dehydrogenase-A (LDHA) expressions which in turn further heightened oxidative stress in CR cells. LDHA knocked-down cells became hypersensitive to riluzole treatments and possessed increased levels of ROS. Addition of NAD(+) re-stabilized LDHA and reversed riluzole induced cell death. Thus far, no drugs are available which could overcome cisplatin resistance or kill cisplatin resistant cells. CR cells possess high levels of ROS and undergo metabolic reprogramming. These metabolic adaptations can be exploited and targeted by riluzole. Riluzole may serve as a dual-targeting agent by suppression LDHA and blocking xCT antiporter. Repurposing of riluzole should be considered for future treatment of cisplatin resistant lung cancer patients. ; Department of Veterans Affairs, BLR&D Career Development Award-2; NIH/NCI; Woman Cancer Association of the University of Miami Award |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | |
| اللغة: | English |
| تدمد: | 1949-2553 |
| العلاقة: | Publisher version; Koç University Institutional Repository; Wangpaichitr, M., et al. "Exploiting Ros and Metabolic Differences to Kill Cisplatin Resistant Lung Cancer." Oncotarget 8.30 (2017): 49275-92.; http://dx.doi.org/10.18632/oncotarget.17568Test; IR01325.pdf; WoS; Scopus; PubMed; 1K2BX001289; 1R01CA149260; NA; http://libdigitalcollections.ku.edu.tr/cdm/ref/collection/IR/id/4661Test |
| DOI: | 10.18632/oncotarget.17568 |
| الإتاحة: | https://doi.org/10.18632/oncotarget.17568Test http://libdigitalcollections.ku.edu.tr/cdm/ref/collection/IR/id/4661Test |
| رقم الانضمام: | edsbas.4CE2D48F |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19492553 |
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| DOI: | 10.18632/oncotarget.17568 |