High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells
Cancer stem cells (CSCs) are relevant therapeutic targets for cancer treatment. Still, the molecular circuits behind CSC characteristics are not fully understood. The low number of CSCs can sometimes be an obstacle to carrying out assays that explore their properties. Thus, increasing CSC numbers vi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/17/4406 |
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| author | Diana Pádua Paula Figueira Mariana Pinto André Filipe Maia Joana Peixoto Raquel T. Lima António Pombinho Carlos Filipe Pereira Raquel Almeida Patrícia Mesquita |
| author_facet | Diana Pádua Paula Figueira Mariana Pinto André Filipe Maia Joana Peixoto Raquel T. Lima António Pombinho Carlos Filipe Pereira Raquel Almeida Patrícia Mesquita |
| author_sort | Diana Pádua |
| collection | DOAJ |
| description | Cancer stem cells (CSCs) are relevant therapeutic targets for cancer treatment. Still, the molecular circuits behind CSC characteristics are not fully understood. The low number of CSCs can sometimes be an obstacle to carrying out assays that explore their properties. Thus, increasing CSC numbers via small molecule-mediated cellular reprogramming appears to be a valid alternative tool. Using the SORE6-GFP reporter system embedded in gastric non-CSCs (SORE6−), we performed a high-throughput image-based drug screen with 1200 small molecules to identify compounds capable of converting SORE6− to SORE6+ (CSCs). Here, we report that the antifungal agent ciclopirox olamine (CPX), a potential candidate for drug repurposing in cancer treatment, is able to reprogram gastric non-CSCs into cancer stem-like cells via activation of SOX2 expression and increased expression of C-MYC, HIF-1α, KLF4, and HMGA1. This reprogramming depends on the CPX concentration and treatment duration. CPX can also induce cellular senescence and the metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis. We also disclose that the mechanism underlying the cellular reprogramming is similar to that of cobalt chloride (CoCl<sub>2</sub>), a hypoxia-mimetic agent. |
| first_indexed | 2024-03-10T23:27:07Z |
| format | Article |
| id | doaj.art-d42f1af7759a4202ba6a3ef78622ee5f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T23:27:07Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d42f1af7759a4202ba6a3ef78622ee5f2023-11-19T07:57:20ZengMDPI AGCancers2072-66942023-09-011517440610.3390/cancers15174406High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like CellsDiana Pádua0Paula Figueira1Mariana Pinto2André Filipe Maia3Joana Peixoto4Raquel T. Lima5António Pombinho6Carlos Filipe Pereira7Raquel Almeida8Patrícia Mesquita9i3S—Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugali3S—Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugali3S—Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugali3S—Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugali3S—Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugali3S—Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugali3S—Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugali3S—Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugali3S—Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, PortugalCancer stem cells (CSCs) are relevant therapeutic targets for cancer treatment. Still, the molecular circuits behind CSC characteristics are not fully understood. The low number of CSCs can sometimes be an obstacle to carrying out assays that explore their properties. Thus, increasing CSC numbers via small molecule-mediated cellular reprogramming appears to be a valid alternative tool. Using the SORE6-GFP reporter system embedded in gastric non-CSCs (SORE6−), we performed a high-throughput image-based drug screen with 1200 small molecules to identify compounds capable of converting SORE6− to SORE6+ (CSCs). Here, we report that the antifungal agent ciclopirox olamine (CPX), a potential candidate for drug repurposing in cancer treatment, is able to reprogram gastric non-CSCs into cancer stem-like cells via activation of SOX2 expression and increased expression of C-MYC, HIF-1α, KLF4, and HMGA1. This reprogramming depends on the CPX concentration and treatment duration. CPX can also induce cellular senescence and the metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis. We also disclose that the mechanism underlying the cellular reprogramming is similar to that of cobalt chloride (CoCl<sub>2</sub>), a hypoxia-mimetic agent.https://www.mdpi.com/2072-6694/15/17/4406gastric cancercancer stem cellsciclopiroxcellular reprogrammingtranscription factorscellular senescence |
| spellingShingle | Diana Pádua Paula Figueira Mariana Pinto André Filipe Maia Joana Peixoto Raquel T. Lima António Pombinho Carlos Filipe Pereira Raquel Almeida Patrícia Mesquita High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells Cancers gastric cancer cancer stem cells ciclopirox cellular reprogramming transcription factors cellular senescence |
| title | High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells |
| title_full | High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells |
| title_fullStr | High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells |
| title_full_unstemmed | High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells |
| title_short | High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells |
| title_sort | high throughput drug screening revealed that ciclopirox olamine can engender gastric cancer stem like cells |
| topic | gastric cancer cancer stem cells ciclopirox cellular reprogramming transcription factors cellular senescence |
| url | https://www.mdpi.com/2072-6694/15/17/4406 |
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