PRMT5 Selective Inhibitor Enhances Therapeutic Efficacy of Cisplatin in Lung Cancer Cells
As a therapeutic approach, epigenetic modifiers have the potential to enhance the efficacy of chemotherapeutic agents. Protein arginine methyltransferase 5 (PRMT5), highly expressed in lung adenocarcinoma, was identified to be involved in tumorigenesis. In the current study, we examined the potentia...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/11/6131 |
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| author | Khuloud Bajbouj Rakhee K. Ramakrishnan Maha Saber-Ayad Hany A. Omar Narjes Saheb Sharif-Askari Jasmin Shafarin Adel B. Elmoselhi Ahmed Ihmaid Suhib AlHaj Ali Abdulla Alalool Reem Abdullah Qutayba Hamid |
| author_facet | Khuloud Bajbouj Rakhee K. Ramakrishnan Maha Saber-Ayad Hany A. Omar Narjes Saheb Sharif-Askari Jasmin Shafarin Adel B. Elmoselhi Ahmed Ihmaid Suhib AlHaj Ali Abdulla Alalool Reem Abdullah Qutayba Hamid |
| author_sort | Khuloud Bajbouj |
| collection | DOAJ |
| description | As a therapeutic approach, epigenetic modifiers have the potential to enhance the efficacy of chemotherapeutic agents. Protein arginine methyltransferase 5 (PRMT5), highly expressed in lung adenocarcinoma, was identified to be involved in tumorigenesis. In the current study, we examined the potential antineoplastic activity of PRMT5 inhibitor, arginine methyltransferase inhibitor 1 (AMI-1), and cisplatin on lung adenocarcinoma. Bioinformatic analyses identified apoptosis, DNA damage, and cell cycle progression as the main PRMT5-associated functional pathways, and survival analysis linked the increased PRMT5 gene expression to worse overall survival in lung adenocarcinoma. Combined AMI-1 and cisplatin treatment significantly reduced cell viability and induced apoptosis. Cell cycle arrest in A549 and DMS 53 cells was evident after AMI-1, and was reinforced after combination treatment. Western blot analysis showed a reduction in demethylation histone 4, a PRMT5- downstream target, after treatment with AMI-1 alone or in combination with cisplatin. While the combination approach tackled lung cancer cell survival, it exhibited cytoprotective abilities on HBEpC (normal epithelial cells). The survival of normal bronchial epithelial cells was not affected by using AMI-1. This study highlights evidence of novel selective antitumor activity of AMI-1 in combination with cisplatin in lung adenocarcinoma cells. |
| first_indexed | 2024-03-10T10:39:27Z |
| format | Article |
| id | doaj.art-cd491b35137d4f2cbf07cce2f4c7fccb |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:39:27Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cd491b35137d4f2cbf07cce2f4c7fccb2023-11-21T23:03:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012211613110.3390/ijms22116131PRMT5 Selective Inhibitor Enhances Therapeutic Efficacy of Cisplatin in Lung Cancer CellsKhuloud Bajbouj0Rakhee K. Ramakrishnan1Maha Saber-Ayad2Hany A. Omar3Narjes Saheb Sharif-Askari4Jasmin Shafarin5Adel B. Elmoselhi6Ahmed Ihmaid7Suhib AlHaj Ali8Abdulla Alalool9Reem Abdullah10Qutayba Hamid11College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesCollege of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesCollege of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab EmiratesCollege of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab EmiratesCollege of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesCollege of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesCollege of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesCollege of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesCollege of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesCollege of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesAs a therapeutic approach, epigenetic modifiers have the potential to enhance the efficacy of chemotherapeutic agents. Protein arginine methyltransferase 5 (PRMT5), highly expressed in lung adenocarcinoma, was identified to be involved in tumorigenesis. In the current study, we examined the potential antineoplastic activity of PRMT5 inhibitor, arginine methyltransferase inhibitor 1 (AMI-1), and cisplatin on lung adenocarcinoma. Bioinformatic analyses identified apoptosis, DNA damage, and cell cycle progression as the main PRMT5-associated functional pathways, and survival analysis linked the increased PRMT5 gene expression to worse overall survival in lung adenocarcinoma. Combined AMI-1 and cisplatin treatment significantly reduced cell viability and induced apoptosis. Cell cycle arrest in A549 and DMS 53 cells was evident after AMI-1, and was reinforced after combination treatment. Western blot analysis showed a reduction in demethylation histone 4, a PRMT5- downstream target, after treatment with AMI-1 alone or in combination with cisplatin. While the combination approach tackled lung cancer cell survival, it exhibited cytoprotective abilities on HBEpC (normal epithelial cells). The survival of normal bronchial epithelial cells was not affected by using AMI-1. This study highlights evidence of novel selective antitumor activity of AMI-1 in combination with cisplatin in lung adenocarcinoma cells.https://www.mdpi.com/1422-0067/22/11/6131PRMT5lung cancerepigeneticscisplatinhistoneHBEpC |
| spellingShingle | Khuloud Bajbouj Rakhee K. Ramakrishnan Maha Saber-Ayad Hany A. Omar Narjes Saheb Sharif-Askari Jasmin Shafarin Adel B. Elmoselhi Ahmed Ihmaid Suhib AlHaj Ali Abdulla Alalool Reem Abdullah Qutayba Hamid PRMT5 Selective Inhibitor Enhances Therapeutic Efficacy of Cisplatin in Lung Cancer Cells International Journal of Molecular Sciences PRMT5 lung cancer epigenetics cisplatin histone HBEpC |
| title | PRMT5 Selective Inhibitor Enhances Therapeutic Efficacy of Cisplatin in Lung Cancer Cells |
| title_full | PRMT5 Selective Inhibitor Enhances Therapeutic Efficacy of Cisplatin in Lung Cancer Cells |
| title_fullStr | PRMT5 Selective Inhibitor Enhances Therapeutic Efficacy of Cisplatin in Lung Cancer Cells |
| title_full_unstemmed | PRMT5 Selective Inhibitor Enhances Therapeutic Efficacy of Cisplatin in Lung Cancer Cells |
| title_short | PRMT5 Selective Inhibitor Enhances Therapeutic Efficacy of Cisplatin in Lung Cancer Cells |
| title_sort | prmt5 selective inhibitor enhances therapeutic efficacy of cisplatin in lung cancer cells |
| topic | PRMT5 lung cancer epigenetics cisplatin histone HBEpC |
| url | https://www.mdpi.com/1422-0067/22/11/6131 |
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