Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy
The dysregulation of Notch signaling is associated with a wide variety of different human cancers. Notch signaling activation mostly relies on the activity of the γ-secretase enzyme that cleaves the Notch receptors and releases the active intracellular domain. It is well-documented that γ-secretase...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/4/972 |
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| author | Maryam Ghanbari-Movahed Zahra Ghanbari-Movahed Saeideh Momtaz Kaitlyn L. Kilpatrick Mohammad Hosein Farzaei Anupam Bishayee |
| author_facet | Maryam Ghanbari-Movahed Zahra Ghanbari-Movahed Saeideh Momtaz Kaitlyn L. Kilpatrick Mohammad Hosein Farzaei Anupam Bishayee |
| author_sort | Maryam Ghanbari-Movahed |
| collection | DOAJ |
| description | The dysregulation of Notch signaling is associated with a wide variety of different human cancers. Notch signaling activation mostly relies on the activity of the γ-secretase enzyme that cleaves the Notch receptors and releases the active intracellular domain. It is well-documented that γ-secretase inhibitors (GSIs) block the Notch activity, mainly by inhibiting the oncogenic activity of this pathway. To date, several GSIs have been introduced clinically for the treatment of various diseases, such as Alzheimer’s disease and various cancers, and their impacts on Notch inhibition have been found to be promising. Therefore, GSIs are of great interest for cancer therapy. The objective of this review is to provide a systematic review of in vitro and in vivo studies for investigating the effect of GSIs on various cancer stem cells (CSCs), mainly by modulation of the Notch signaling pathway. Various scholarly electronic databases were searched and relevant studies published in the English language were collected up to February 2020. Herein, we conclude that GSIs can be potential candidates for CSC-targeting therapy. The outcome of our study also indicates that GSIs in combination with anticancer drugs have a greater inhibitory effect on CSCs. |
| first_indexed | 2024-03-09T00:56:41Z |
| format | Article |
| id | doaj.art-8710733fc298417283b0780903f4e3f3 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T00:56:41Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8710733fc298417283b0780903f4e3f32023-12-11T16:50:34ZengMDPI AGMolecules1420-30492021-02-0126497210.3390/molecules26040972Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer StrategyMaryam Ghanbari-Movahed0Zahra Ghanbari-Movahed1Saeideh Momtaz2Kaitlyn L. Kilpatrick3Mohammad Hosein Farzaei4Anupam Bishayee5Medical Technology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, IranMedical Biology Research Center, Kermanshah University of Medical sciences, Kermanshah 6714415185, IranMedicinal Plants Research Center, Institute of Medicinal Plants, Academic Center for Education, Culture and Research, Tehran 1417614411, IranLake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USAMedical Technology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, IranLake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USAThe dysregulation of Notch signaling is associated with a wide variety of different human cancers. Notch signaling activation mostly relies on the activity of the γ-secretase enzyme that cleaves the Notch receptors and releases the active intracellular domain. It is well-documented that γ-secretase inhibitors (GSIs) block the Notch activity, mainly by inhibiting the oncogenic activity of this pathway. To date, several GSIs have been introduced clinically for the treatment of various diseases, such as Alzheimer’s disease and various cancers, and their impacts on Notch inhibition have been found to be promising. Therefore, GSIs are of great interest for cancer therapy. The objective of this review is to provide a systematic review of in vitro and in vivo studies for investigating the effect of GSIs on various cancer stem cells (CSCs), mainly by modulation of the Notch signaling pathway. Various scholarly electronic databases were searched and relevant studies published in the English language were collected up to February 2020. Herein, we conclude that GSIs can be potential candidates for CSC-targeting therapy. The outcome of our study also indicates that GSIs in combination with anticancer drugs have a greater inhibitory effect on CSCs.https://www.mdpi.com/1420-3049/26/4/972cancer stem cellsγ-secretaseγ-secretase inhibitorsNotch signalingcancer treatment |
| spellingShingle | Maryam Ghanbari-Movahed Zahra Ghanbari-Movahed Saeideh Momtaz Kaitlyn L. Kilpatrick Mohammad Hosein Farzaei Anupam Bishayee Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy Molecules cancer stem cells γ-secretase γ-secretase inhibitors Notch signaling cancer treatment |
| title | Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy |
| title_full | Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy |
| title_fullStr | Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy |
| title_full_unstemmed | Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy |
| title_short | Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy |
| title_sort | unlocking the secrets of cancer stem cells with γ secretase inhibitors a novel anticancer strategy |
| topic | cancer stem cells γ-secretase γ-secretase inhibitors Notch signaling cancer treatment |
| url | https://www.mdpi.com/1420-3049/26/4/972 |
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