{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:51:47Z","timestamp":1790268707193,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T00:00:00Z","timestamp":1586217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["17H06401"],"award-info":[{"award-number":["17H06401"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The NF\u2010kappa B (NF\u2010\u03baB) pathway plays a pivotal role in tumor progression and chemoresistance, and its inhibition has been shown to suppress tumor growth in a variety of preclinical models. Recently, we succeeded in synthesizing a water\u2010soluble injectable type of curcumin \u03b2\u2010D\u2010glucuronide (CMG), which is converted into a free\u2010form of curcumin by \u03b2\u2010glucuronidase in vivo. Herein, we aimed to clarify the efficacy, safety and pharmacokinetics of CMG in a xenograft mouse model. First, we confirmed that the presence of KRAS\/TP53 mutations significantly increased the IC<jats:sub>50<\/jats:sub> of oxaliplatin (L\u2010OHP) and NF\u2010\u03baB activity in HCT116 cells in vitro. Then, we tested the efficacy of CMG in an HCT116 colon cancer xenograft mice model. CMG demonstrated superior anticancer effects compared to L\u2010OHP in an L\u2010OHP\u2010resistant xenograft model. With regard to safety, significant bodyweight loss, severe myelosuppression and AST\/ALT elevation were observed in L\u2010OHP\u2010treated mice, whereas none of these toxicity was noted in CMG\u2010treated mice. The combination of CMG and L\u2010OHP exhibited additive effects in these xenograft models without increasing toxicity. Pharmacokinetic analysis revealed that high levels of free\u2010form curcumin were maintained in the tumor tissue after 48\u00a0hours following CMG administration, but it was not detected in other major organs, such as the heart, liver and spleen. Immunohistochemistry revealed reduced NF\u2010\u03baB activity in the tumor tissue extracted from CMG\u2010treated mice compared with that from control mice. These results indicated that CMG could be a promising anticancer prodrug for treating colon cancer with minimal toxicity.<\/jats:p>","DOI":"10.1111\/cas.14383","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T13:22:46Z","timestamp":1584019366000},"page":"1785-1793","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Curcumin \u03b2\u2010D\u2010glucuronide exhibits anti\u2013tumor effects on oxaliplatin\u2010resistant colon cancer with less toxicity in vivo"],"prefix":"10.1111","volume":"111","author":[{"given":"Hitomi","family":"Ozawa\u2010Umeta","sequence":"first","affiliation":[{"name":"Therabiopharma Inc. Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuhiro","family":"Kishimoto","sequence":"additional","affiliation":[{"name":"Therabiopharma Inc. 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