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Whether and how taurine protects human ovarian cancer (OC) cells from DNA damage caused by cisplatin is not well understood. We found that OC ascites-derived cells contained significantly more intracellular taurine than cell culture-modeled OC. In culture, elevation of intracellular taurine concentration to OC ascites-cell-associated levels suppressed proliferation of various OC cell lines and patient-derived organoids, reduced glycolysis, and induced cell protection from cisplatin. Taurine cell protection was associated with decreased DNA damage in response to cisplatin. A combination of RNA sequencing, reverse-phase protein arrays, live-cell microscopy, flow cytometry, and biochemical validation experiments provided evidence for taurine-mediated induction of mutant or wild-type p53 binding to DNA, activation of p53 effectors involved in negative regulation of the cell cycle (p21), and glycolysis (TIGAR). Paradoxically, taurine\u2019s suppression of cell proliferation was associated with activation of pro-mitogenic signal transduction including ERK, mTOR, and increased mRNA expression of major DNA damage-sensing molecules such as DNAPK, ATM and ATR. While inhibition of ERK or p53 did not interfere with taurine\u2019s ability to protect cells from cisplatin, suppression of mTOR with Torin2, a clinically relevant inhibitor that also targets DNAPK and ATM\/ATR, broke taurine\u2019s cell protection. Our studies implicate that elevation of intracellular taurine could suppress cell growth and metabolism, and activate cell protective mechanisms involving mTOR and DNA damage-sensing signal transduction.<\/jats:p>","DOI":"10.3390\/nu16121816","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T08:49:03Z","timestamp":1718009343000},"page":"1816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Modeling of Intracellular Taurine Levels Associated with Ovarian Cancer Reveals Activation of p53, ERK, mTOR and DNA-Damage-Sensing-Dependent Cell Protection"],"prefix":"10.3390","volume":"16","author":[{"given":"Daniel","family":"Centeno","sequence":"first","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ 07030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadaf","family":"Farsinejad","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ 07030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Kochetkova","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institute, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Volpari","sequence":"additional","affiliation":[{"name":"The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4144-7706","authenticated-orcid":false,"given":"Aleksandra","family":"Gladych-Macioszek","sequence":"additional","affiliation":[{"name":"Department of Reproduction, University Gynaecology and Obstetrics Hospital, 60-502 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5028-1408","authenticated-orcid":false,"given":"Agnieszka","family":"Klupczynska-Gabryszak","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry, Pozna\u0144 University of Medical Sciences, 61-701 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teagan","family":"Polotaye","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ 07030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ 07030, 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Karolinska Institute, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5711-5883","authenticated-orcid":false,"suffix":"Jr.","given":"Frederick","family":"Monsma","sequence":"additional","affiliation":[{"name":"The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Muller","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Durham University, Durham DH1 3LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9993-1504","authenticated-orcid":false,"given":"Jan","family":"Matysiak","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry, Pozna\u0144 University of Medical Sciences, 61-701 Pozna\u0144, 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Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2677-1025","authenticated-orcid":false,"given":"Laura","family":"Martin","sequence":"additional","affiliation":[{"name":"The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8375-8447","authenticated-orcid":false,"given":"Marcin","family":"Iwanicki","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ 07030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1093\/hmg\/ddz303","article-title":"Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter 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