Article ; Online: Targeting notch signaling pathway in breast cancer stem cells through drug repurposing approach.
2022 Volume 27, Issue 6, Page(s) 2431–2440
Abstract: Breast cancer is recognized globally as one of the leading causes of malignant morbidity. It is a heterogeneous disease that accounts for 30 percent of all women diagnosed with cancer. To bring an anti-cancer drug from the bench to the bedside is an ... ...
| Abstract | Breast cancer is recognized globally as one of the leading causes of malignant morbidity. It is a heterogeneous disease that accounts for 30 percent of all women diagnosed with cancer. To bring an anti-cancer drug from the bench to the bedside is an expensive and time-consuming process. The drug repurposing approach targets new enemies (new diseases) with old weapons (known drugs). The present study identified an FDA-approved drug targeting the γ-secretase complex involved in the Notch signaling pathway in breast cancer stem cells (BCSCs). A literature survey and in-silico study identified Venetoclax as a γ-secretase inhibitor (GSI) from 1615 FDA-approved drug compounds. In-silico docking potential of Venetoclax was better than the standard γ-secretase inhibitor RO4929097. Also, the molecular dynamics simulations of 200 ns confirmed the stability of the Venetoclax-γ-secretase complex. These findings suggest that the use of Venetoclax represents a potential γ-secretase inhibitor in breast cancer stem cells. Eventually, the in vitro and clinical evaluation will be needed to confirm the potential chemopreventive and treatment effects of Venetoclax against breast cancer and breast cancer stem cells. Venetoclax appeared as the most promising drug of the 1615 FDA-approved drugs. Our in-silico findings suggest that Venetoclax may act as a γ-secretase inhibitor against the Notch signaling pathway in breast cancer stem cells. |
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| MeSH term(s) | Female ; Humans ; Breast Neoplasms/metabolism ; Receptors, Notch/metabolism ; Amyloid Precursor Protein Secretases ; Drug Repositioning ; Signal Transduction ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology |
| Chemical Substances | venetoclax (N54AIC43PW) ; Receptors, Notch ; Amyloid Precursor Protein Secretases (EC 3.4.-) |
| Language | English |
| Publishing date | 2022-11-14 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 1376507-3 |
| ISSN | 1573-501X ; 1381-1991 |
| ISSN (online) | 1573-501X |
| ISSN | 1381-1991 |
| DOI | 10.1007/s11030-022-10561-y |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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