Academic Journal
Synergistic targeting of TrxR1 and ATM/AKT pathway in human colon cancer cells
| العنوان: | Synergistic targeting of TrxR1 and ATM/AKT pathway in human colon cancer cells |
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| المؤلفون: | Xin Shen, Yiqun Xia, Hui Lu, Peisen Zheng, Junqi Wang, Yinghua Chen, Chenxin Xu, Chenyu Qiu, Yafei Zhang, Zhongxiang Xiao, Peng Zou, Ri Cui, Daoyong Ni |
| المصدر: | Biomedicine & Pharmacotherapy, Vol 174, Iss , Pp 116507- (2024) |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2024 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | TrxR1, AKT, ROS, Autophagy, Colon cancer, Therapeutics. Pharmacology, RM1-950 |
| الوصف: | Thioredoxin reductase 1 (TrxR1) has emerged as a promising target for cancer therapy. In our previous research, we discovered several new TrxR1 inhibitors and found that they all have excellent anti-tumor activity. At the same time, we found these TrxR1 inhibitors all lead to an increase in AKT phosphorylation in cancer cells, but the detailed role of AKT phosphorylation in TrxR1 inhibitor-mediated cell death remains unclear. In this study, we identified the combination of AKT and TrxR1 inhibitor displayed a strong synergistic effect in colon cancer cells. Furthermore, we demonstrated that the synergistic effect of auranofin (TrxR1 inhibitor) and MK-2206 (AKT inhibitor) was caused by ROS accumulation. Importantly, we found that ATM inhibitor KU-55933 can block the increase of AKT phosphorylation caused by auranofin, and exhibited a synergistic effect with auranofin. Taken together, our study demonstrated that the activation of ATM/AKT pathway is a compensatory mechanism to cope with ROS accumulation induced by TrxR1 inhibitor, and synergistic targeting of TrxR1 and ATM/AKT pathway is a promising strategy for treating colon cancer. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0753-3322 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S0753332224003913; https://doaj.org/toc/0753-3322; https://doaj.org/article/77b46d5963d443848810f8ec8b3ba891 |
| DOI: | 10.1016/j.biopha.2024.116507 |
| الاتاحة: | https://doi.org/10.1016/j.biopha.2024.116507 https://doaj.org/article/77b46d5963d443848810f8ec8b3ba891 |
| رقم الانضمام: | edsbas.6B1450A8 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 07533322 |
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| DOI: | 10.1016/j.biopha.2024.116507 |