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The molecule is synthesized by aminoglycoside phosphotransferase enzyme in the presence of aminoglycosides. ADAADi interacts with ATP-dependent chromatin remodeling proteins through motif Ia present in the conserved helicase domain, and thus, can potentially inhibit all members of this family of proteins. We show that mammalian cells are sensitive to ADAADi but with variable responses in different cell lines. ADAADi can be generated from a wide variety of aminoglycosides; however, cells showed differential response to ADAADi generated from various aminoglycosides. Using HeLa and DU145 cells as model system we have explored the effect of ADAADi on cellular functions. We show that the transcriptional network of a cell type is altered when treated with sub-lethal concentration of ADAADi. Although ADAADi has no known effects on DNA chemical and structural integrity, expression of DNA-damage response genes was altered. The transcripts encoding for the pro-apoptotic proteins were found to be upregulated while the anti-apoptotic genes were found to be downregulated. This was accompanied by increased apoptosis leading us to hypothesize that the ADAADi treatment promotes apoptotic-type of cell death by upregulating the transcription of pro-apoptotic genes. ADAADi also inhibited migration of cells as well as their colony forming ability leading us to conclude that the compound has effective anti-tumor properties.<\/jats:p>","DOI":"10.1371\/journal.pone.0251354","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T13:24:08Z","timestamp":1621257848000},"page":"e0251354","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Altering mammalian transcription networking with ADAADi: An inhibitor of ATP-dependent chromatin remodeling"],"prefix":"10.1371","volume":"16","author":[{"given":"Radhakrishnan","family":"Rakesh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Upasana Bedi","family":"Chanana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saddam","family":"Hussain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soni","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaveri","family":"Goel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepa","family":"Bisht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ketki","family":"Patne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pynskhem Bok","family":"Swer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel W.","family":"Hockensmith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0559-9484","authenticated-orcid":true,"given":"Rohini","family":"Muthuswami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"pone.0251354.ref001","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/cr.2011.32","article-title":"ATP-dependent chromatin remodeling: genetics, genomics and mechanisms","volume":"21","author":"DC Hargreaves","year":"2011","journal-title":"Cell Res"},{"key":"pone.0251354.ref002","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1093\/nar\/gkl295","article-title":"Identification of multiple distinct Snf2 subfamilies with conserved structural motifs","volume":"34","author":"A Flaus","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"pone.0251354.ref003","doi-asserted-by":"crossref","first-page":"919","DOI":"10.2217\/epi-2017-0034","article-title":"The BRG1 ATPase of human SWI\/SNF chromatin remodeling enzymes as a driver of cancer","volume":"9","author":"Q Wu","year":"2017","journal-title":"Epigenomics"},{"key":"pone.0251354.ref004","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1002\/1097-4652(200101)186:1<136::AID-JCP1010>3.0.CO;2-4","article-title":"Characterization of SWI\/SNF protein expression in human breast cancer cell lines and other malignancies","volume":"186","author":"MF Decristofaro","year":"2001","journal-title":"J Cell Physiol"},{"key":"pone.0251354.ref005","first-page":"6171","article-title":"BRG1, a component of the SWI-SNF complex, is mutated in multiple human tumor cell lines","volume":"60","author":"AK Wong","year":"2000","journal-title":"Cancer Res"},{"key":"pone.0251354.ref006","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1038\/sj.onc.1204331","article-title":"When the SWI\/SNF complex remodels\u2026the cell cycle","volume":"20","author":"C Muchardt","year":"2001","journal-title":"Oncogene"},{"key":"pone.0251354.ref007","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0092-8674(00)00030-1","article-title":"BRCA1 is associated with a human SWI\/SNF-related complex: linking chromatin remodeling to breast cancer","volume":"102","author":"DA Bochar","year":"2000","journal-title":"Cell"},{"key":"pone.0251354.ref008","first-page":"560","article-title":"Loss of BRG1\/BRM in human lung cancer cell lines and primary lung cancers: correlation with poor prognosis","volume":"63","author":"DN Reisman","year":"2003","journal-title":"Cancer Res"},{"key":"pone.0251354.ref009","first-page":"3865","article-title":"The SMARCA2\/4 ATPase Domain Surpasses the Bromodomain as a Drug Target in SWI\/SNF-Mutant Cancers: Insights from cDNA Rescue and PFI-3","volume":"75","author":"B Vangamudi","year":"2015","journal-title":"Inhibitor Studies. 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