Pharmacologic downregulation of protein arginine methyltransferase1 expression by adenosine dialdehyde increases cell senescence in breast cancer
We investigated the role of protein arginine methylation (PAM) in estrogen receptor (ER)-positive breast cancer cells through pharmacological intervention. Tamoxifen (TAM) or adenosine dialdehyde (ADOX), independently, triggered cell cycle arrest and down-regulated PAM, as reduced protein arginine m...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Elsevier BV
2020
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| Online Access: | http://psasir.upm.edu.my/id/eprint/94569/ |
| _version_ | 1848862033714348032 |
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| author | Singh, Priya Charles, Soniya Madhavan, Thirumurthy Munusamy-Ramanujam, Ganesh Saraswathi, Nambiappan T. Arasu, Mariadhas Valan Al-Dhabi, Naif Abdullah Arshad, Aziz Arockiaraj, Jesu Mala, Kanchana |
| author_facet | Singh, Priya Charles, Soniya Madhavan, Thirumurthy Munusamy-Ramanujam, Ganesh Saraswathi, Nambiappan T. Arasu, Mariadhas Valan Al-Dhabi, Naif Abdullah Arshad, Aziz Arockiaraj, Jesu Mala, Kanchana |
| author_sort | Singh, Priya |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | We investigated the role of protein arginine methylation (PAM) in estrogen receptor (ER)-positive breast cancer cells through pharmacological intervention. Tamoxifen (TAM) or adenosine dialdehyde (ADOX), independently, triggered cell cycle arrest and down-regulated PAM, as reduced protein arginine methyltransferase1 (PRMT1) mRNA and asymmetric dimethylarginine (ADMA) levels. Synergistic effect of these compounds elicited potent anti-cancer effect. However, reduction in ADMA was not proportionate with the compound-induced down-regulation of PRMT1 mRNA. We hypothesized that the disproportionate effect is due to the influence of the compounds on other methyltransferases, which catalyze the arginine dimethylation reaction and the diversity in the degree of drug-protein interaction among these methyltransferases. In silico analyses revealed that independently, ADOX or TAM, binds with phosphatidylethanolamine-methyltransferase (PEMT) or betaine homocysteine-methyl transferase (BHMT); and that the binding affinity of ADOX with PEMT or BHMT is prominent than TAM. These observations suggest that in breast cancer, synergistic effect of ADOX + TAM elicits impressive protective function by regulating PAM; and plausibly, restoration of normal enzyme activities of methyltransferases catalyzing arginine dimethylation could have clinical benefits. |
| first_indexed | 2025-11-15T13:10:36Z |
| format | Article |
| id | upm-94569 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-15T13:10:36Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-945692022-12-05T03:49:13Z http://psasir.upm.edu.my/id/eprint/94569/ Pharmacologic downregulation of protein arginine methyltransferase1 expression by adenosine dialdehyde increases cell senescence in breast cancer Singh, Priya Charles, Soniya Madhavan, Thirumurthy Munusamy-Ramanujam, Ganesh Saraswathi, Nambiappan T. Arasu, Mariadhas Valan Al-Dhabi, Naif Abdullah Arshad, Aziz Arockiaraj, Jesu Mala, Kanchana We investigated the role of protein arginine methylation (PAM) in estrogen receptor (ER)-positive breast cancer cells through pharmacological intervention. Tamoxifen (TAM) or adenosine dialdehyde (ADOX), independently, triggered cell cycle arrest and down-regulated PAM, as reduced protein arginine methyltransferase1 (PRMT1) mRNA and asymmetric dimethylarginine (ADMA) levels. Synergistic effect of these compounds elicited potent anti-cancer effect. However, reduction in ADMA was not proportionate with the compound-induced down-regulation of PRMT1 mRNA. We hypothesized that the disproportionate effect is due to the influence of the compounds on other methyltransferases, which catalyze the arginine dimethylation reaction and the diversity in the degree of drug-protein interaction among these methyltransferases. In silico analyses revealed that independently, ADOX or TAM, binds with phosphatidylethanolamine-methyltransferase (PEMT) or betaine homocysteine-methyl transferase (BHMT); and that the binding affinity of ADOX with PEMT or BHMT is prominent than TAM. These observations suggest that in breast cancer, synergistic effect of ADOX + TAM elicits impressive protective function by regulating PAM; and plausibly, restoration of normal enzyme activities of methyltransferases catalyzing arginine dimethylation could have clinical benefits. Elsevier BV 2020-11 Article PeerReviewed Singh, Priya and Charles, Soniya and Madhavan, Thirumurthy and Munusamy-Ramanujam, Ganesh and Saraswathi, Nambiappan T. and Arasu, Mariadhas Valan and Al-Dhabi, Naif Abdullah and Arshad, Aziz and Arockiaraj, Jesu and Mala, Kanchana (2020) Pharmacologic downregulation of protein arginine methyltransferase1 expression by adenosine dialdehyde increases cell senescence in breast cancer. European Journal of Pharmacology, 891. art. no. 173697. pp. 1-18. ISSN 0014-2999; ESSN: 1879-0712 https://www.sciencedirect.com/science/article/pii/S0014299920307895 10.1016/j.ejphar.2020.173697 |
| spellingShingle | Singh, Priya Charles, Soniya Madhavan, Thirumurthy Munusamy-Ramanujam, Ganesh Saraswathi, Nambiappan T. Arasu, Mariadhas Valan Al-Dhabi, Naif Abdullah Arshad, Aziz Arockiaraj, Jesu Mala, Kanchana Pharmacologic downregulation of protein arginine methyltransferase1 expression by adenosine dialdehyde increases cell senescence in breast cancer |
| title | Pharmacologic downregulation of protein arginine methyltransferase1 expression by adenosine dialdehyde increases cell senescence in breast cancer |
| title_full | Pharmacologic downregulation of protein arginine methyltransferase1 expression by adenosine dialdehyde increases cell senescence in breast cancer |
| title_fullStr | Pharmacologic downregulation of protein arginine methyltransferase1 expression by adenosine dialdehyde increases cell senescence in breast cancer |
| title_full_unstemmed | Pharmacologic downregulation of protein arginine methyltransferase1 expression by adenosine dialdehyde increases cell senescence in breast cancer |
| title_short | Pharmacologic downregulation of protein arginine methyltransferase1 expression by adenosine dialdehyde increases cell senescence in breast cancer |
| title_sort | pharmacologic downregulation of protein arginine methyltransferase1 expression by adenosine dialdehyde increases cell senescence in breast cancer |
| url | http://psasir.upm.edu.my/id/eprint/94569/ http://psasir.upm.edu.my/id/eprint/94569/ http://psasir.upm.edu.my/id/eprint/94569/ |