Small molecule inhibitor of nicotinamide N-methyltransferase shows anti-proliferative activity in HeLa cells

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dc.authorid0000-0001-5518-5004en_US
dc.contributor.authorAkar, Serra
dc.contributor.authorDuran, Tuğçe
dc.contributor.authorAzzawri, Ali Ahmed
dc.contributor.authorKoçak, Nadir
dc.contributor.authorÇelik, Çetin
dc.contributor.authorYıldırım, Halil İbrahim
dc.date.accessioned2022-06-02T11:49:59Z
dc.date.available2022-06-02T11:49:59Z
dc.date.issued2021en_US
dc.departmentDicle Üniversitesi, Veteriner Fakültesi, Zootekni ve Hayvan Besleme Bölümü, Zootekn Ana Bilim Dalıen_US
dc.descriptionWOS:000623839300001
dc.descriptionPMID: 33645410
dc.description.abstractThe anti-proliferative effects of 5-methylquinolinium (5MQ) of nicotinamide N-methyltransferase (NNMT) have not been previously investigated on a cervical cancer cell line. NNMT is a metabolic enzyme that is correlated with tumour progression and metastasis. 5MQ is a small molecule inhibitor of NNMT. 0.1-500 mu M of 5MQ was tested on the HeLa epithelial cervical cancer cell line. Cell viability was assessed with the MTT test. TWIST, ZEB1, SERPIN1, SIRT1, CD16, mRNA and various protein expression levels were analysed with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western Blotting, respectively. 5MQ significantly inhibited HeLa cell proliferation in a concentration and time-dependent manner. Increased cell shrinkage, loss of cellular adhesions and apoptotic bodies were observed in HeLa cells after 5MQ treatment. Following treatment with 5MQ, ZEB1, SIRT1, CD16 mRNA levels were increased while TWIST and SERPIN1 mRNA levels were reduced. Expressions of oncogenic proteins phospho-Akt and SIRT1 were decreased. 5MQ can effectively inhibit HeLa cell proliferation without apparently affecting HEK-293 cell proliferation. IMPACT STATEMENT What is already known on this subject? NNMT is a cytosolic enzyme involved in tumour progression, metastasis and treatment resistance. It was overexpressed in many human malignancies. 5-amino-1-methylquinolinium (5MQ) is a novel small molecule inhibitor of NNMT that has shown promising results in the treatment of obesity and in senescent muscle regeneration. 5MQ has not been tested on the HeLa cervical cancer cell line, previously. What do the results of this study add? In this study, 5MQ was tested on the HeLa cervical cancer cell line for the first time and the molecular changes associated with 5MQ treatment were analysed. 5MQ demonstrated significant anti-proliferative activity on HeLa cells, which displayed morphological signs of apoptosis. Treatment of HeLa cells with 5MQ led to an increase in ZEB1, SIRT1 mRNA while TWIST mRNA was decreased. Phospho-Akt and Sirtuin1 protein expressions were decreased. What are the implications of these findings for clinical practice and/or further research? 5MQ can effectively inhibit HeLa cell proliferation without apparently affecting HEK-293 cell proliferation. 5MQ treatment was associated with a decrease in the expression of phospho-Akt and Sirtuin1 proteins, both of which have been reported to maintain tumour progression. 5MQ can further be investigated and modified for anti-cancer therapy.en_US
dc.identifier.citationAkar, S., Duran, T., Azzawri, A.A., Koçak, N., Çelik, Ç. ve Yıldırım, H.İ. (2021). Small molecule inhibitor of nicotinamide N-methyltransferase shows anti-proliferative activity in HeLa cells. Journal of Obstetrics and Gynaecology,41(8), 1240-1245.en_US
dc.identifier.doi10.1080/01443615.2020.1854696
dc.identifier.endpage1245en_US
dc.identifier.issn0144-3615
dc.identifier.issn1364-6893
dc.identifier.issue8en_US
dc.identifier.pmid33645410
dc.identifier.scopus2-s2.0-85101864100
dc.identifier.scopusqualityQ3
dc.identifier.startpage1240en_US
dc.identifier.urihttps://hdl.handle.net/11468/9953
dc.identifier.volume41en_US
dc.identifier.wosWOS:000623839300001
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorAzzawri, Ali Ahmed
dc.institutionauthorYıldırım, Halil İbrahim
dc.language.isoenen_US
dc.publisherTaylor & Francisen_US
dc.relation.ispartofJournal of Obstetrics and Gynaecology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectCervical canceren_US
dc.subjectNicotinamide N-methyltransferaseen_US
dc.subject5-amino-1-methylquinoliniumen_US
dc.subjectPhospho-Aktsirtuin1en_US
dc.titleSmall molecule inhibitor of nicotinamide N-methyltransferase shows anti-proliferative activity in HeLa cellsen_US
dc.titleSmall molecule inhibitor of nicotinamide N-methyltransferase shows anti-proliferative activity in HeLa cells
dc.typeArticleen_US

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