{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:36:55Z","timestamp":1760060215797,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Previously, we established gemcitabine (Gem)-resistant pancreatic cancer (PaCa) cell lines and showed that the acquisition of Gem resistance is accompanied by enhanced activation of the inflammatory transcription factor nuclear factor-\u03baB (NF-\u03baB). In this study, we focus on CalebinA, a natural compound derived from the rhizomes of turmeric, known for its potent anti-inflammatory properties. It has been suggested that this compound may exert anticancer effects by downregulating the NF-\u03baB signaling cascade. Therefore, we collaborated with Sabinsa Corporation, Japan, to explore its potential application in pancreatic cancer therapy. Methods: We used gemcitabine-resistant pancreatic cell lines to demonstrate the effect of CalebinA on cell toxicity, invasiveness, cytokine levels, NF-\u03baB p65 activity, and tube formation in angiogenesis. Tumor volume and histopathological analysis were used to analyze the effects of CalebinA on tumors induced by the subcutaneous injection of pancreatic cell lines in mice. Results: Treatment with 10 \u03bcM CalebinA significantly inhibited NF-\u03baB activity. Gem-resistant PaCa cells exhibited higher invasive and angiogenic capacities than non-resistant parental cells; however, these capacities were markedly suppressed by CalebinA. In vivo, intraperitoneal CalebinA administration every 3 days led to a significant reduction in tumor volume in mice bearing subcutaneous xenografts of the AsPC-1 pancreatic cancer cell line. Immunohistochemical analysis revealed that CalebinA suppressed the expression of Ki-67, CD31-positive microvessel density, and NF-\u03baB p65. Conclusions: These findings suggest that CalebinA holds promise as a novel therapeutic agent for Gem-resistant pancreatic cancer and may be a strong candidate for clinical application.<\/jats:p>","DOI":"10.3390\/nu17162641","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T15:16:37Z","timestamp":1755184597000},"page":"2641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Natural Compound CalebinA Suppresses Gemcitabine Resistance and Tumor Progression by Inhibiting Angiogenesis and Invasion Through NF-\u03baB Signaling in Pancreatic Cancer"],"prefix":"10.3390","volume":"17","author":[{"given":"Yuki","family":"Eguchi","sequence":"first","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9654-6080","authenticated-orcid":false,"given":"Yoichi","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, East Medical Center, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuriko","family":"Uehara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saburo","family":"Sugita","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Denda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Nonoyama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromichi","family":"Murase","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomokatsu","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenta","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takafumi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Sagawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yushi","family":"Yamakawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Mitsui","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuji","family":"Takiguchi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"ref_1","unstructured":"National Cancer Center Japan (2024, February 17). 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