{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:01:50Z","timestamp":1784952110429,"version":"3.55.0"},"reference-count":19,"publisher":"Pharmaceutical Society of Japan","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biological &amp; Pharmaceutical Bulletin","Biol. Pharm. Bull."],"published-print":{"date-parts":[[2026,7,24]]},"DOI":"10.1248\/bpb.b26-00297","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T22:11:24Z","timestamp":1784844684000},"page":"1161-1168","source":"Crossref","is-referenced-by-count":0,"title":["A Phenylbutyrate-Derived Nitric Oxide Donor Induces Pancreatic Cancer Cell Death Accompanied by Impairment of Autophagy-Related Pathways and HIF-1&lt;i&gt;\u03b1&lt;\/i&gt; Reduction"],"prefix":"10.1248","volume":"49","author":[{"given":"Kaho","family":"Takasaki","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University, 4\u201322\u20131 Ikeda, Nishi-ku, Kumamoto 860\u20130082, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuro","family":"Beppu","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University, 4\u201322\u20131 Ikeda, Nishi-ku, Kumamoto 860\u20130082, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Imoto","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University, 4\u201322\u20131 Ikeda, Nishi-ku, Kumamoto 860\u20130082, Japan"},{"name":"DDS Research Institute, Sojo University, 4\u201322\u20131 Ikeda, Nishi-ku, Kumamoto 860\u20130082, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Tsukigawa","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University, 4\u201322\u20131 Ikeda, Nishi-ku, Kumamoto 860\u20130082, Japan"},{"name":"DDS Research Institute, Sojo University, 4\u201322\u20131 Ikeda, Nishi-ku, Kumamoto 860\u20130082, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Tokuno","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University, 4\u201322\u20131 Ikeda, Nishi-ku, Kumamoto 860\u20130082, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Otagiri","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University, 4\u201322\u20131 Ikeda, Nishi-ku, Kumamoto 860\u20130082, Japan"},{"name":"DDS Research Institute, Sojo University, 4\u201322\u20131 Ikeda, Nishi-ku, Kumamoto 860\u20130082, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keishi","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University, 4\u201322\u20131 Ikeda, Nishi-ku, Kumamoto 860\u20130082, Japan"},{"name":"DDS Research Institute, Sojo University, 4\u201322\u20131 Ikeda, Nishi-ku, Kumamoto 860\u20130082, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Ueno-Shuto","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University, 4\u201322\u20131 Ikeda, Nishi-ku, Kumamoto 860\u20130082, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Nishi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Sojo University, 4\u201322\u20131 Ikeda, Nishi-ku, Kumamoto 860\u20130082, Japan"},{"name":"DDS Research Institute, Sojo University, 4\u201322\u20131 Ikeda, Nishi-ku, Kumamoto 860\u20130082, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"163","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1) Hori M, Matsuda T, Shibata A, Katanoda K, Sobue T, Nishimoto H. Cancer incidence and incidence rates in Japan in 2009: a study of 32 population-based cancer registries for the monitoring of cancer incidence in Japan (MCIJ) project. <i>Jpn. J. Clin. Oncol.<\/i>, <b>45<\/b>, 884\u2013891 (2015).","DOI":"10.1093\/jjco\/hyv088"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Conroy T, Desseigne F, Ychou M, Bouch\u00e9 O, Guimbaud R, B\u00e9couarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardi\u00e8re C, Bennouna J, Bachet JB, Khemissa-Akouz F, P\u00e9r\u00e9-Verg\u00e9 D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M. FOLFIRINOX <i>versus<\/i> gemcitabine for metastatic pancreatic cancer. <i>N. Engl. J. Med.<\/i>, <b>364<\/b>, 1817\u20131825 (2011).","DOI":"10.1056\/NEJMoa1011923"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Von Hoff DD, Ervin T, Arena FP, <i>et al<\/i>. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. <i>N. Engl. J. Med.<\/i>, <b>369<\/b>, 1691\u20131703 (2013).","DOI":"10.1056\/NEJMoa1304369"},{"key":"4","unstructured":"4) Olive KP, Jacobetz MA, Davidson CJ, <i>et al<\/i>. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. <i>Science<\/i>, <b>324<\/b>, 1457\u20131461 (2009)."},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Provenzano PP, Cuevas C, Chang AE, Goel VK, Von Hoff DD, Hingorani SR. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. <i>Cancer Cell<\/i>, <b>21<\/b>, 418\u2013429 (2012).","DOI":"10.1016\/j.ccr.2012.01.007"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Semenza GL. Hypoxia-inducible factors in physiology and medicine. <i>Cell<\/i>, <b>148<\/b>, 399\u2013408 (2012).","DOI":"10.1016\/j.cell.2012.01.021"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H, Bause A, Li Y, Stommel JM, Dell\u2019Antonio G, Mautner J, Tonon G, Haigis M, Shirihai OS, Doglioni C, Bardeesy N, Kimmelman AC. Pancreatic cancers require autophagy for tumor growth. <i>Genes Dev.<\/i>, <b>25<\/b>, 717\u2013729 (2011).","DOI":"10.1101\/gad.2016111"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) New M, Van Acker T, Long JS, Sakamaki J, Ryan KM, Tooze SA. Molecular pathways controlling autophagy in pancreatic cancer. <i>Front. Oncol.<\/i>, <b>7<\/b>, 28 (2017).","DOI":"10.3389\/fonc.2017.00028"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Huang Z, Fu J, Zhang Y. Nitric oxide donor-based cancer therapy: advances and prospects. <i>J. Med. Chem.<\/i>, <b>60<\/b>, 7617\u20137635 (2017).","DOI":"10.1021\/acs.jmedchem.6b01672"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Beppu T, Nishi K, Imoto S, Araki W, Setoguchi I, Ueda A, Suetsugi N, Ishima Y, Ikeda T, Otagiri M, Yamasaki K. Novel nitric oxide donor, nitrated phenylbutyrate, induces cell death of human pancreatic cancer cells and suppresses tumor growth of cancer xenografts. <i>Oncol. Rep.<\/i>, <b>48<\/b>, 178 (2022).","DOI":"10.3892\/or.2022.8393"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Kaizuka T, Morishita H, Hama Y, Tsukamoto S, Matsui T, Toyota Y, Kodama A, Ishihara T, Mizushima T, Mizushima N. An autophagic flux probe that releases an internal control. <i>Mol. Cell<\/i>, <b>64<\/b>, 835\u2013849 (2016).","DOI":"10.1016\/j.molcel.2016.09.037"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Kim SE, Park HJ, Jeong HK, Kim MJ, Kim M, Bae ON, Baek SH. Autophagy sustains the survival of human pancreatic cancer PANC-1 cells under extreme nutrient deprivation conditions. <i>Biochem. Biophys. Res. Commun.<\/i>, <b>463<\/b>, 205\u2013210 (2015).","DOI":"10.1016\/j.bbrc.2015.05.022"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Mizushima N, Yoshimori T, Levine B. Methods in mammalian autophagy research. <i>Cell<\/i>, <b>140<\/b>, 313\u2013326 (2010).","DOI":"10.1016\/j.cell.2010.01.028"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Oh CK, Dolatabadi N, Cieplak P, Diaz-Meco MT, Moscat J, Nolan JP, Nakamura T, Lipton SA. S-Nitrosylation of p62 inhibits autophagic flux to promote \u03b1-synuclein secretion and spread in Parkinson\u2019s disease and Lewy body dementia. <i>J. Neurosci.<\/i>, <b>42<\/b>, 3011\u20133024 (2022).","DOI":"10.1523\/JNEUROSCI.1508-21.2022"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Kim KR, Cho EJ, Eom JW, Oh SS, Nakamura T, Oh CK, Lipton SA, Kim YH. S-Nitrosylation of cathepsin B affects autophagic flux and accumulation of protein aggregates in neurodegenerative disorders. <i>Cell Death Differ.<\/i>, <b>29<\/b>, 2137\u20132150 (2022).","DOI":"10.1038\/s41418-022-01004-0"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Papandreou I, Lim AL, Laderoute K, Denko NC. Hypoxia signals autophagy in tumor cells <i>via<\/i> AMPK activity, independent of HIF-1, BNIP3, and BNIP3L. <i>Cell Death Differ.<\/i>, <b>15<\/b>, 1572\u20131581 (2008).","DOI":"10.1038\/cdd.2008.84"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Semenza GL. Targeting HIF-1 for cancer therapy. <i>Nat. Rev. Cancer<\/i>, <b>3<\/b>, 721\u2013732 (2003).","DOI":"10.1038\/nrc1187"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) S\u0142otwi\u0144ski R, S\u0142otwi\u0144ska SM. Pancreatic cancer and adaptive metabolism in a nutrient-deficient environment. <i>Cent. Eur. J. Immunol.<\/i>, <b>46<\/b>, 388\u2013394 (2021).","DOI":"10.5114\/ceji.2021.109693"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Sun S, Kim MJ, Omar AM, Duy Phan N, Aoike M, Awale S. GDP induces PANC-1 human pancreatic cancer cell death preferentially under nutrient starvation by inhibiting PI3K\/Akt\/mTOR\/autophagy signaling pathway. <i>Chem. Biodivers.<\/i>, <b>18<\/b>, e2100389 (2021).","DOI":"10.1002\/cbdv.202100389"}],"container-title":["Biological and Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/49\/7\/49_b26-00297\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T03:23:04Z","timestamp":1784949784000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/49\/7\/49_b26-00297\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":19,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1248\/bpb.b26-00297","relation":{},"ISSN":["0918-6158","1347-5215"],"issn-type":[{"value":"0918-6158","type":"print"},{"value":"1347-5215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]},"article-number":"b26-00297"}}