التفاصيل البيبلوغرافية
| العنوان: |
Identification of the targeted therapeutic potential of doxycycline for a subset of gastric cancer patients |
| المؤلفون: |
Pandian, Jaishree, Panneerpandian, Ponmathi, Devanandan, Helen Jemimah, Sekar, Balaji T., Balakrishnan, Karthik, Selvarasu, Karthikeyan, Muthupandi, Karthikeyan, Ganesan, Kumaresan |
| المصدر: |
Annals of the New York Academy of Sciences ; volume 1467, issue 1, page 94-111 ; ISSN 0077-8923 1749-6632 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2020 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
The identification of new drugs for the targeted therapy of gastric cancer remains an important need. The RAS/RAF/MEK/ERK/ELK1 signaling cascade is activated in many cancers, including gastric cancer. To identify the targetable inhibitors of the ERK/MAPK pathway, we performed a repurposing screening of a panel of antimicrobial agents in gastric cancer cells using an ERK/MAPK‐driven firefly luciferase reporter assay. Multiple antibiotics were identified to inhibit ERK‐mediated transcriptional activity. Among them, doxycycline showed high inhibition of ERK/MAPK‐regulated transcriptional activity and the levels of ERK proteins. Doxycycline was further identified to inhibit the proliferation and the colony‐ and spheroid‐forming potential of gastric cancer cells. By in vitro signaling pathway and genome‐wide expression profiling analyses, doxycycline was identified to inhibit signaling pathways and transcriptional activities regulated by ER, Myc, E2F1, Wnt, SMAD2/3/4, Notch, and OCT4. Doxycycline was also found to activate p53‐, ATF6‐, NRF1/2‐, and MTF1‐mediated transcription and inhibit the transcription of histones, proteasomal genes, fibroblast growth factor, and other oncogenic factors. These observations show the multitargeting and targeted therapeutic features of doxycycline for a subset of gastric tumors. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1111/nyas.14288 |
| الإتاحة: |
https://doi.org/10.1111/nyas.14288Test |
| حقوق: |
http://onlinelibrary.wiley.com/termsAndConditions#vorTest |
| رقم الانضمام: |
edsbas.EC87B14F |
| قاعدة البيانات: |
BASE |
