{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:58:41Z","timestamp":1785560321827,"version":"3.56.0"},"reference-count":46,"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":[[2026,7,28]]},"DOI":"10.1248\/bpb.b26-00307","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T22:11:39Z","timestamp":1785190299000},"page":"1174-1181","source":"Crossref","is-referenced-by-count":0,"title":["A Curcumin Analog, 3,5-Bis(2\u2032-ethoxybenzylidene)-piperidine-4-one (E145), Suppresses NF-&lt;i&gt;\u03ba&lt;\/i&gt;B Signaling to Inhibit Breast Cancer Growth and Metastasis"],"prefix":"10.1248","volume":"49","author":[{"given":"Sana","family":"Jabbar","sequence":"first","affiliation":[{"name":"Section of Host Defences, Institute of Natural Medicine, University of Toyama, Toyama 930\u20130194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cancer Cell Biology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930\u20130194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiya","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Section of Host Defences, Institute of Natural Medicine, University of Toyama, Toyama 930\u20130194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka","family":"He","sequence":"additional","affiliation":[{"name":"Section of Host Defences, Institute of Natural Medicine, University of Toyama, Toyama 930\u20130194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sisca","family":"Ucche","sequence":"additional","affiliation":[{"name":"Section of Host Defences, Institute of Natural Medicine, University of Toyama, Toyama 930\u20130194, Japan"},{"name":"Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Ritmaleni","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia"},{"name":"Curcumin Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Ichiro","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Section of Host Defences, Institute of Natural Medicine, University of Toyama, Toyama 930\u20130194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"Section of Host Defences, Institute of Natural Medicine, University of Toyama, Toyama 930\u20130194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"163","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1) Prasad S, Gupta SC, Tyagi AK, Aggarwal BB. Curcumin, a component of golden spice: From bedside to bench and back. <i>Biotechnol. Adv.<\/i>, <b>32<\/b>, 1053\u20131064 (2014).","DOI":"10.1016\/j.biotechadv.2014.04.004"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Kocaadam B, \u015eanlier N. Curcumin, an active component of turmeric (<i>Curcuma longa<\/i>), and its effects on health. <i>Crit. Rev. Food Sci. Nutr.<\/i>, <b>57<\/b>, 2889\u20132895 (2017).","DOI":"10.1080\/10408398.2015.1077195"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Wilken R, Veena MS, Wang MB, Srivatsan ES. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. <i>Mol. Cancer<\/i>, <b>10<\/b>, 12 (2011).","DOI":"10.1186\/1476-4598-10-12"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Mukhopadhyay A, Bueso-Ramos C, Chatterjee D, Pantazis P, Aggarwal BB. Curcumin downregulates cell survival mechanisms in human prostate cancer cell lines. <i>Oncogene<\/i>, <b>20<\/b>, 7597\u20137609 (2001).","DOI":"10.1038\/sj.onc.1204997"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Liu S, Wang Z, Hu Z, Zeng X, Li Y, Su Y, Zhang C, Ye Z. Anti-tumor activity of curcumin against androgen-independent prostate cancer cells <i>via<\/i> inhibition of NF-\u03baB and AP-1 pathway <i>in vitro<\/i>. <i>J. Huazhong Univ. Sci. Technol. Med. Sci.<\/i>, <b>31<\/b>, 530\u2013534 (2011).","DOI":"10.1007\/s11596-011-0485-1"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Hussain Z, Thu HE, Amjad MW, Hussain F, Ahmed TA, Khan S. Exploring recent developments to improve antioxidant, anti-inflammatory and antimicrobial efficacy of curcumin: A review of new trends and future perspectives. <i>Mater. Sci. Eng. C Mater. Biol. Appl.<\/i>, <b>77<\/b>, 1316\u20131326 (2017).","DOI":"10.1016\/j.msec.2017.03.226"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Fadus MC, Lau C, Bikhchandani J, Lynch HT. Curcumin: an age-old anti-inflammatory and anti-neoplastic agent. <i>J. Tradit. Complement. Med.<\/i>, <b>7<\/b>, 339\u2013346 (2016).","DOI":"10.1016\/j.jtcme.2016.08.002"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Salehi B, Stojanovi\u0107-Radi\u0107 Z, Mateji\u0107 J, Sharifi-Rad M, Anil Kumar NV, Martins N, Sharifi-Rad J. The therapeutic potential of curcumin: a review of clinical trials. <i>Eur. J. Med. Chem.<\/i>, <b>163<\/b>, 527\u2013545 (2019).","DOI":"10.1016\/j.ejmech.2018.12.016"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Chen QY, Zheng Y, Jiao DM, Chen FY, Hu HZ, Wu YQ, Song J, Yan J, Wu LJ, Lv GY. Curcumin inhibits lung cancer cell migration and invasion through Rac1-dependent signaling pathway. <i>J. Nutr. Biochem.<\/i>, <b>25<\/b>, 177\u2013185 (2014).","DOI":"10.1016\/j.jnutbio.2013.10.004"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Liu T, Long T, Li H. Curcumin suppresses the proliferation of oral squamous cell carcinoma through a specificity protein 1\/nuclear factor-\u03baB-dependent pathway. <i>Exp. Ther. Med.<\/i>, <b>21<\/b>, 202 (2021).","DOI":"10.3892\/etm.2021.9635"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. <i>Mol. Pharm.<\/i>, <b>4<\/b>, 807\u2013818 (2007).","DOI":"10.1021\/mp700113r"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Dei Cas M, Ghidoni R. Dietary curcumin: correlation between bioavailability and health potential. <i>Nutrients<\/i>, <b>11<\/b>, 2147 (2019).","DOI":"10.3390\/nu11092147"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Obeagu EI, Obeagu GU. Breast cancer: a review of risk factors and diagnosis. <i>Medicine<\/i>, <b>103<\/b>, e36905 (2024).","DOI":"10.1097\/MD.0000000000036905"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Grimm D. Recent advances in breast cancer research. <i>Int. J. Mol. Sci.<\/i>, <b>24<\/b>, 11990 (2023).","DOI":"10.3390\/ijms241511990"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Xiong N, Wu H, Yu Z. Advancements and challenges in triple-negative breast cancer: a comprehensive review of therapeutic and diagnostic strategies. <i>Front. Oncol.<\/i>, <b>14<\/b>, 1405491 (2024).","DOI":"10.3389\/fonc.2024.1405491"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Al-Mahmood S, Sapiezynski J, Garbuzenko OB, Minko T. Metastatic and triple-negative breast cancer: challenges and treatment options. <i>Drug Deliv. Transl. Res.<\/i>, <b>8<\/b>, 1483\u20131507 (2018).","DOI":"10.1007\/s13346-018-0551-3"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Xiong X, Zheng LW, Ding Y, Chen YF, Cai YW, Wang LP, Huang L, Liu CC, Shao ZM, Yu KD. Breast cancer: pathogenesis and treatments. <i>Signal Transduct. Target. Ther.<\/i>, <b>10<\/b>, 49 (2025).","DOI":"10.1038\/s41392-024-02108-4"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Riggio AI, Varley KE, Welm AL. The lingering mysteries of metastatic recurrence in breast cancer. <i>Br. J. Cancer<\/i>, <b>124<\/b>, 13\u201326 (2021).","DOI":"10.1038\/s41416-020-01161-4"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Xu Y, Gong M, Wang Y, Yang Y, Liu S, Zeng Q. Global trends and forecasts of breast cancer incidence and deaths. <i>Sci. Data<\/i>, <b>10<\/b>, 334 (2023).","DOI":"10.1038\/s41597-023-02253-5"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Wang W, Nag SA, Zhang R. Targeting the NF\u03baB signaling pathways for breast cancer prevention and therapy. <i>Curr. Med. Chem.<\/i>, <b>22<\/b>, 264\u2013289 (2015).","DOI":"10.2174\/0929867321666141106124315"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Khongthong P, Roseweir AK, Edwards J. The NF-KB pathway and endocrine therapy resistance in breast cancer. <i>Endocr. Relat. Cancer<\/i>, <b>26<\/b>, R369\u2013R380 (2019).","DOI":"10.1530\/ERC-19-0087"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Guo Q, Jin Y, Lin M, Zeng C, Zhang J. NF-\u03baB signaling in therapy resistance of breast cancer: mechanisms, approaches, and challenges. <i>Life Sci.<\/i>, <b>348<\/b>, 122684 (2024).","DOI":"10.1016\/j.lfs.2024.122684"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Al-Mutairi MS, Habashy HO. Nuclear factor-\u03baB clinical significance in breast cancer: an immunohistochemical study. <i>Med. Princ. Pract.<\/i>, <b>32<\/b>, 33\u201339 (2023).","DOI":"10.1159\/000527828"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Pavitra E, Kancharla J, Gupta VK, Prasad K, Sung JY, Kim J, Tej MB, Choi R, Lee JH, Han YK, Raju GS, Bhaskar L, Huh YS. The role of NF-\u03baB in breast cancer initiation, growth, metastasis, and resistance to chemotherapy. <i>Biomed. Pharmacother.<\/i>, <b>163<\/b>, 114822 (2023).","DOI":"10.1016\/j.biopha.2023.114822"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Jabbar S, Ucche S, Irshad FM, Seephan S, Sasaki SI, Murwanti R, Ritmaleni, Hayakawa Y. Identification of 3,5-bis (2-ethoxybenzylidene) piperidin-4-one as a monocarbonyl curcumin analog inhibiting cell-intrinsic NF-\u03baB activity in 4T1 breast cancer cells. <i>Biol. Pharm. Bull.<\/i>, <b>49<\/b>, 725\u2013731 (2026).","DOI":"10.1248\/bpb.b25-00785"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Abdellatef AA, Meselhy MR, El-Askary HI, El-mekkawy S, Hayakawa Y. Anti-metastatic function of triterpene phytochemicals from guggul by targeting tumor-intrinsic  NF-\u03baB activation in triple-negative breast cancer cells. <i>Phytomed. Plus<\/i>, <b>2<\/b>, 100345 (2022).","DOI":"10.1016\/j.phyplu.2022.100345"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Abdellatef AA, Zhou Y, Yamada A, Elmekkawy SA, Kohyama A, Yokoyama S, Meselhy MR, Matsuya Y, Sakurai H, Hayakawa Y. Synthetic E-guggulsterone derivative GSD-1 inhibits NF-\u03baB signaling and suppresses the metastatic potential of breast cancer cells. <i>Biomed. Pharmacother.<\/i>, <b>140<\/b>, 111737 (2021).","DOI":"10.1016\/j.biopha.2021.111737"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Murwanti R, Rahmadani A, Hermawan A, Ari Sudarmanto BS. Curcumin inhibits vascular endothelial growth factor (VEGF) expression on a murine triple-negative breast cancer. <i>AIP Conference Proceedings<\/i>. Vol. 2260, No. 1, American Institute of Physics Inc., p. 060020 (2020).","DOI":"10.1063\/5.0016425"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Murwanti R,Rahmadani A, Kholifah E, Hermawan A, Ari Sudarmanto BS. Effect of curcumin on MMP-9 activity of 4T1 murine triple-negative breast cancer cells. <i>AIP Conference Proceedings<\/i>, Vol. 2260, 060017 (2020).","DOI":"10.1063\/5.0016424"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Nagaraju GP, Benton L, Bethi SR, Shoji M, El-Rayes BF. Curcumin analogs: their roles in pancreatic cancer growth and metastasis. <i>Int. J. Cancer<\/i>, <b>145<\/b>, 10\u201319 (2019).","DOI":"10.1002\/ijc.31867"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Nagargoje AA, Deshmukh TR, Shaikh MH, Khedkar VM, Shingate BB. Anticancer perspectives of monocarbonyl analogs of curcumin: a decade (2014\u20132024) review. <i>Arch. Pharm.<\/i>, <b>357<\/b>, 2400197 (2024).","DOI":"10.1002\/ardp.202400197"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32) Pan Z, Chen C, Zhou Y, Xu F, Xu Y. Synthesis and cytotoxic evaluation of monocarbonyl analogs of curcumin as potential anti-tumor agents. <i>Drug Dev. Res.<\/i>, <b>77<\/b>, 43\u201349 (2016).","DOI":"10.1002\/ddr.21291"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Liu Z, Tang L, Zou P, Zhang Y, Wang Z, Fang Q, Jiang L, Chen G, Xu Z, Zhang H, Liang G. Synthesis and biological evaluation of allylated and prenylated mono-carbonyl analogs of curcumin as anti-inflammatory agents. <i>Eur. J. Med. Chem.<\/i>, <b>74<\/b>, 671\u2013682 (2014).","DOI":"10.1016\/j.ejmech.2013.10.061"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Chen X, Zhang P, Zhang H, Ma X, Zhang Y, Wu Y, Jin K, Wang J, Wu J. Discovery of cinnamylaldehyde-derived mono-carbonyl curcumin analogs as anti-gastric cancer agents <i>via<\/i> suppression of STAT3 and AKT pathway. <i>Bioorg. Chem.<\/i>, <b>146<\/b>, 107306 (2024).","DOI":"10.1016\/j.bioorg.2024.107306"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35) Abdellatef AA, Fathy M, Mohammed AESI, Bakr MSA, Ahmed AH, Abbass HS, El-Desoky AH, Morita H, Nikaido T, Hayakawa Y. Inhibition of cell-intrinsic NF-\u03baB activity and metastatic abilities of breast cancer by aloe-emodin and emodic-acid isolated from <i>Asphodelus microcarpus<\/i>. <i>J. Nat. Med.<\/i>, <b>75<\/b>, 840\u2013853 (2021).","DOI":"10.1007\/s11418-021-01526-w"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36) Landais I, Hiddingh S, McCarroll M, Yang C, Sun A, Turker MS, Snyder JP, Hoatlin ME. Monoketone analogs of curcumin, a new class of Fanconi anemia pathway inhibitors. <i>Mol. Cancer<\/i>, <b>8<\/b>, 133 (2009).","DOI":"10.1186\/1476-4598-8-133"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37) Mohammed F, Rashid-Doubell F, Taha S, Cassidy S, Fredericks S. Effects of curcumin complexes on MDA-MB-231 breast cancer cell proliferation. <i>Int. J. Oncol.<\/i>, <b>57<\/b>, 445\u2013455 (2020).","DOI":"10.3892\/ijo.2020.5065"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38) Saeed MEM, Y\u00fccer R, Dawood M, Hegazy MEF, Drif A, Ooko E, Kadioglu O, Seo EJ, Kamounah FS, Titinchi SJ, Bachmeier B, Efferth T. <i>In silico<\/i> and <i>in vitro<\/i> screening of 50 curcumin compounds as EGFR and NF-\u03baB inhibitors. <i>Int. J. Mol. Sci.<\/i>, <b>23<\/b>, 3966 (2022).","DOI":"10.3390\/ijms23073966"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39) Peng Y, Zheng J, Zhou Y, Li J. Characterization of a novel curcumin analog P1 as potent inhibitor of the NF-\u03baB signaling pathway with distinct mechanisms. <i>Acta Pharmacol. Sin.<\/i>, <b>34<\/b>, 939\u2013950 (2013).","DOI":"10.1038\/aps.2013.2"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40) Hibino S, Kawazoe T, Kasahara H, Itoh S, Ishimoto T, Sakata-Yanagimoto M, Taniguchi K. Inflammation-induced tumorigenesis and metastasis. <i>Int. J. Mol. Sci.<\/i>, <b>22<\/b>, 5421 (2021).","DOI":"10.3390\/ijms22115421"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41) Sahu PK. Design, structure activity relationship, cytotoxicity and evaluation of antioxidant activity of curcumin derivatives\/analogues. <i>Eur. J. Med. Chem.<\/i>, <b>121<\/b>, 510\u2013516 (2016).","DOI":"10.1016\/j.ejmech.2016.05.037"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42) Lozada-Garc\u00eda MC, Enr\u00edquez RG, Ram\u00edrez-Ap\u00e1n TO, Nieto-Camacho A, Palacios-Espinosa JF, Custodio-Galv\u00e1n Z, Soria-Arteche O, P\u00e9rez-Villanueva J. Synthesis of curcuminoids and evaluation of their cytotoxic and antioxidant properties. <i>Molecules<\/i>, <b>22<\/b>, 633 (2017).","DOI":"10.3390\/molecules22040633"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43) Biswas S, Chen S, Liang G, Feng B, Cai L, Khan ZA, Chakrabarti S. Curcumin analogs reduce stress and inflammation indices in experimental models of diabetes. <i>Front. Endocrinol.<\/i>, <b>10<\/b>, 887 (2019).","DOI":"10.3389\/fendo.2019.00887"},{"key":"44","doi-asserted-by":"crossref","unstructured":"44) Liang G, Li X, Chen L, Yang S, Wu X, Studer E, Gurley E, Hylemon PB, Ye F, Li Y, Zhou H. Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin. <i>Bioorg. Med. Chem. Lett.<\/i>, <b>18<\/b>, 1525\u20131529 (2008).","DOI":"10.1016\/j.bmcl.2007.12.068"},{"key":"45","doi-asserted-by":"crossref","unstructured":"45) Mohankumar K, Sridharan S, Pajaniradje S, Singh VK, Ronsard L, Banerjea AC, Somasundaram DB, Coumar MS, Periyasamy L, Rajagopalan R. BDMC-A, an analog of curcumin, inhibits markers of invasion, angiogenesis, and metastasis in breast cancer cells <i>via<\/i> NF-\u03baB pathway\u2014a comparative study with curcumin. <i>Biomed. Pharmacother.<\/i>, <b>74<\/b>, 178\u2013186 (2015).","DOI":"10.1016\/j.biopha.2015.07.024"},{"key":"46","doi-asserted-by":"crossref","unstructured":"46) Kasinski AL, Du Y, Thomas SL, Zhao J, Sun SY, Khuri FR, Wang CY, Shoji M, Sun A, Snyder JP, Liotta D, Fu H. Inhibition of I\u03baB kinase-nuclear factor-\u03baB signaling pathway by 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24), a novel monoketone analog of curcumin. <i>Mol. Pharmacol.<\/i>, <b>74<\/b>, 654\u2013661 (2008).","DOI":"10.1124\/mol.108.046201"}],"container-title":["Biological and Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/49\/7\/49_b26-00307\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:23:52Z","timestamp":1785558232000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/49\/7\/49_b26-00307\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":46,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1248\/bpb.b26-00307","relation":{},"ISSN":["0918-6158","1347-5215"],"issn-type":[{"value":"0918-6158","type":"print"},{"value":"1347-5215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]},"article-number":"b26-00307"}}