{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:27:31Z","timestamp":1780392451562,"version":"3.54.1"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>\n                    Poly(ADP\u2010ribose) glycohydrolase (PARG) is a key enzyme involved in poly(ADP\u2010ribose) (PAR) degradation and is considered a potential anticancer target. We previously investigated resistance mechanisms to the PARG inhibitor PDD00017273 in human colorectal cancer HCT116 cells and established an acquired PDD00017273\u2010resistant HCT116R\n                    <jats:sup>PDD<\/jats:sup>\n                    cell line. In this study, we analyzed the protein levels of enzymes associated with PAR metabolism in both parental HCT116 cells and resistant HCT116R\n                    <jats:sup>PDD<\/jats:sup>\n                    cells using western blotting. PARG expression levels were similar between HCT116R\n                    <jats:sup>PDD<\/jats:sup>\n                    and HCT116 cells. However, the levels of PARP1 and ARH3 were reduced in HCT116R\n                    <jats:sup>PDD<\/jats:sup>\n                    cells compared to HCT116 cells. Nevertheless, intracellular PAR levels were elevated in HCT116R\n                    <jats:sup>PDD<\/jats:sup>\n                    cells. Interestingly, HCT116R\n                    <jats:sup>PDD<\/jats:sup>\n                    cells exhibited greater sensitivity to \u03b3\u2010ray irradiation and the nicotinamide phosphoribosyltransferase (NAMPT) inhibitor FK866 than the parental HCT116 cells, yet showed comparable sensitivity to 5\u2010FU, cisplatin, and PARP inhibitors olaparib, talazoparib, and veliparib. Furthermore, we observed that HCT116R\n                    <jats:sup>PDD<\/jats:sup>\n                    cells tended to maintain slightly higher levels of intracellular NAD\n                    <jats:sup>+<\/jats:sup>\n                    \/NADH and ATP compared to parental HCT116 cells. These findings suggest that cancer cells employ a mechanism to regulate NAD\n                    <jats:sup>+<\/jats:sup>\n                    and ATP levels, thereby avoiding cell death from intracellular PAR accumulation through coordinated PARP\u2013PARG regulation.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.70178","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T12:33:59Z","timestamp":1764938039000},"page":"1020-1029","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Anticancer sensitivities and biological characteristics of\n                    <scp>HCT116<\/scp>\n                    cells resistant to the selective poly(\n                    <scp>ADP<\/scp>\n                    \u2010ribose) glycohydrolase inhibitor"],"prefix":"10.1002","volume":"16","author":[{"given":"Kaede","family":"Tsuda","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmaceutical Sciences Tokyo University of Science  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Ogino","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmaceutical Sciences Tokyo University of Science  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2239-6208","authenticated-orcid":false,"given":"Akira","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmaceutical Sciences Tokyo University of Science  Tokyo 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a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis","volume":"63","author":"Hasmann M","year":"2003","journal-title":"Cancer 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