التفاصيل البيبلوغرافية
| العنوان: |
Anticancer Effect of Verteporfin on Non-Small Cell Lung Cancer via Gradual Reduction of ANO1 Protein Levels |
| المؤلفون: |
Jeong, Sung Baek, Das, Raju, Kim, Dong-hyun, Lee, Sion, Oh, Hye In, Jo, Sungwoo, Kim, Jeongdong, Park, SeonJu, Moon, Uk Yeol, Kwon, Oh-bin, Namkung, Wan, Lee, Sungwoo, Cho, Byoung Chul, Woo, Joohan, Seo, Yohan |
| بيانات النشر: |
Authorea, Inc. |
| سنة النشر: |
2024 |
| المجموعة: |
The Winnower (via CrossRef) |
| الوصف: |
Background and Purpose: Anoctamin 1 (ANO1) is a calcium-activated chloride channel found in various cell types and is overexpressed in non-small cell lung cancer (NSCLC), a major cause of cancer-related mortality. This study aimed to investigate whether verteporfin exerts anticancer effects on non-small cell lung cancer by gradually reducing ANO1 protein levels. Experimental Approach: We screened ANO1 inhibitors for biological activity using high-throughput screening and selected verteporfin. Subsequently, we investigated the effects of verteporfin on NSCLC cells as well as the molecular mechanisms involved. Key Results: Verteporfin reduced ANO1 protein levels but had no effects on its channel function. Verteporfin did not inhibit ANO1-induced chloride secretion but reduced ANO1 protein levels in a dose-dependent manner, with an IC50 value of ~300 nM. Verteporfin inhibited neither P2Y receptor-induced intracellular Ca2+ mobilization nor cystic fibrosis transmembrane conductance regulator (CFTR) channel activity. Molecular docking studies revealed that verteporfin bound to specific sites on ANO1 protein. Interestingly, verteporfin decreased p-EGF receptor levels via reduction of ANO1 protein levels; however, it increased p-ERK1/2 levels. Verteporfin reduced the viability and migration of only ANO1-expressing cells, PC9, and gefitinib-resistant PC9 cells, and induced apoptosis by increasing caspase-3 activity and PARP-1 cleavage; however, it did not affect hERG channel activity. Conclusion and Implications: These results indicate that the main mechanism underlying verteporfin action associated with anticancer activity involves the reduction of ANO1 protein levels. |
| نوع الوثيقة: |
other/unknown material |
| اللغة: |
unknown |
| DOI: |
10.22541/au.170670406.65118309/v1 |
| الإتاحة: |
https://doi.org/10.22541/au.170670406.65118309/v1Test |
| رقم الانضمام: |
edsbas.A0FABA42 |
| قاعدة البيانات: |
BASE |
