Therapeutic effects of guanidine hydrochloride on breast cancer through targeting KCNG1 gene
Background: Triple-negative breast cancer (TNBC) is one of the subtypes of breast cancer (BC) that is associated with poor survival rates and failure to respond to hormonal and targeted therapies. Objective: The aim of this study was to identify a specific gene at the expression level for TNBC and t...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223007722 |
| _version_ | 1797801821553557504 |
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| author | Mehdi Roshanian Bakhsh Leila Rouhi Kamran Ghaedi Mehrdad Hashemi Maryam Peymani Saeed Samarghandian |
| author_facet | Mehdi Roshanian Bakhsh Leila Rouhi Kamran Ghaedi Mehrdad Hashemi Maryam Peymani Saeed Samarghandian |
| author_sort | Mehdi Roshanian Bakhsh |
| collection | DOAJ |
| description | Background: Triple-negative breast cancer (TNBC) is one of the subtypes of breast cancer (BC) that is associated with poor survival rates and failure to respond to hormonal and targeted therapies. Objective: The aim of this study was to identify a specific gene at the expression level for TNBC and targeting of this type of breast cancer based on it. Using TCGA database, genes that are particularly high expression in TNBC subtypes compared to other BC subtypes (in terms of receptor status) and normal samples were identified and their sensitivity and specificity were evaluated. Using PharmacoGX and Drug Bank data, drug sensitivity and drug-appropriate genes were identified, respectively. The effects of the identified drug on triple-negative cell lines (MDA-MB-468) were evaluated in comparison with the cell line of other subtypes (MCF7) by apoptosis and MTS tests. Results: Data analyzes showed that the expression level of KCNG1 gene in the TNBC subgroup was significantly higher compared to other BC subtypes from the KCN gene family and ROC results showed that this gene had highest sensitivity and specificity in TNBC subtype. The results of drug resistance and sensitivity showed that an increase in the expression level of KCNG1 was associated with sensitivity to Cisplatin and Oxaliplatin. Moreover, Drug Bank results showed that Guanidine hydrochloride (GuHCl) was a suitable inhibitor for KCNG1. In vitro results showed that the expression level of KCNG1 was higher in MDA-MB-468 compared to MCF7. In addition, the rate of apoptosis in response to GuHCl treatment in MDA-MB-468 cell line as TNBC cell model was higher than MCF7 in the same concentration. Conclusion: This study revealed that GuHCl could be a suitable treatment for TNBC subtype by targeting of KCNG1. |
| first_indexed | 2024-03-13T04:56:18Z |
| format | Article |
| id | doaj.art-1a841701b63f475fb66adf75a046d4d5 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-13T04:56:18Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-1a841701b63f475fb66adf75a046d4d52023-06-18T05:00:55ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-08-01164114982Therapeutic effects of guanidine hydrochloride on breast cancer through targeting KCNG1 geneMehdi Roshanian Bakhsh0Leila Rouhi1Kamran Ghaedi2Mehrdad Hashemi3Maryam Peymani4Saeed Samarghandian5Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, the Islamic Republic of IranDepartment of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, the Islamic Republic of IranDepartment of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, the Islamic Republic of Iran; Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, the Islamic Republic of IranDepartment of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, the Islamic Republic of Iran; Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, the Islamic Republic of Iran; Corresponding author at: Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, the Islamic Republic of Iran.Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, the Islamic Republic of Iran; Corresponding authors.Healthy Ageing Research Centre, Neyshabur University of Medical Sciences, Neyshabur, the Islamic Republic of Iran; Corresponding authors.Background: Triple-negative breast cancer (TNBC) is one of the subtypes of breast cancer (BC) that is associated with poor survival rates and failure to respond to hormonal and targeted therapies. Objective: The aim of this study was to identify a specific gene at the expression level for TNBC and targeting of this type of breast cancer based on it. Using TCGA database, genes that are particularly high expression in TNBC subtypes compared to other BC subtypes (in terms of receptor status) and normal samples were identified and their sensitivity and specificity were evaluated. Using PharmacoGX and Drug Bank data, drug sensitivity and drug-appropriate genes were identified, respectively. The effects of the identified drug on triple-negative cell lines (MDA-MB-468) were evaluated in comparison with the cell line of other subtypes (MCF7) by apoptosis and MTS tests. Results: Data analyzes showed that the expression level of KCNG1 gene in the TNBC subgroup was significantly higher compared to other BC subtypes from the KCN gene family and ROC results showed that this gene had highest sensitivity and specificity in TNBC subtype. The results of drug resistance and sensitivity showed that an increase in the expression level of KCNG1 was associated with sensitivity to Cisplatin and Oxaliplatin. Moreover, Drug Bank results showed that Guanidine hydrochloride (GuHCl) was a suitable inhibitor for KCNG1. In vitro results showed that the expression level of KCNG1 was higher in MDA-MB-468 compared to MCF7. In addition, the rate of apoptosis in response to GuHCl treatment in MDA-MB-468 cell line as TNBC cell model was higher than MCF7 in the same concentration. Conclusion: This study revealed that GuHCl could be a suitable treatment for TNBC subtype by targeting of KCNG1.http://www.sciencedirect.com/science/article/pii/S0753332223007722TNBCGuanidine hydrochlorideKCNG1Potassium channels |
| spellingShingle | Mehdi Roshanian Bakhsh Leila Rouhi Kamran Ghaedi Mehrdad Hashemi Maryam Peymani Saeed Samarghandian Therapeutic effects of guanidine hydrochloride on breast cancer through targeting KCNG1 gene Biomedicine & Pharmacotherapy TNBC Guanidine hydrochloride KCNG1 Potassium channels |
| title | Therapeutic effects of guanidine hydrochloride on breast cancer through targeting KCNG1 gene |
| title_full | Therapeutic effects of guanidine hydrochloride on breast cancer through targeting KCNG1 gene |
| title_fullStr | Therapeutic effects of guanidine hydrochloride on breast cancer through targeting KCNG1 gene |
| title_full_unstemmed | Therapeutic effects of guanidine hydrochloride on breast cancer through targeting KCNG1 gene |
| title_short | Therapeutic effects of guanidine hydrochloride on breast cancer through targeting KCNG1 gene |
| title_sort | therapeutic effects of guanidine hydrochloride on breast cancer through targeting kcng1 gene |
| topic | TNBC Guanidine hydrochloride KCNG1 Potassium channels |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223007722 |
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