{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T09:51:38Z","timestamp":1777283498910,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Colorectal cancer (CRC) is the second common cause of cancer death in the world and its development can be regulated by herbal compounds. Unfortunately, little information is known about the signal pathways of\n                    <jats:italic>Piper betle<\/jats:italic>\n                    isoeugenol in CRC cells (CRCCs). Using three CRC cell lines (SW480, SW620, and HCT116) that represent different molecular characteristics and serve as in vitro models of CRC progression, we found that isoeugenol inhibited cell growth. Wound healing and Boyden chamber assays indicated that isoeugenol inhibited the migration and invasion in CRCCs. Mechanistically, isoeugenol suppressed key regulators of cell cycle progression and epithelial\u2013mesenchymal transition (EMT), including pAKT, CDK4, CDK6, cyclin D1, N\u2010cadherin, and Snail, while increasing the levels of pAMPK, pJNK, pp38 MAPK, and E\u2010cadherin. Cell line\u2010specific modulation of CDK2, cyclin D3, p21, p27, and pERK proteins was also observed. Furthermore, isoeugenol inhibited the enzymatic activities of MMP\u20102 and MMP\u20109. Pharmacological inhibition of AMPK or p38 antagonized isoeugenol\u2010suppressed cell growth, migration, invasion, and associated signaling events. In conclusion, these data suggest that isoeugenol may inhibit CRCC growth, migration, and invasion through activations of AMPK and p38 MAPK pathways and modulating pathways involved in cell cycle regulation and EMT.\n                  <\/jats:p>","DOI":"10.1002\/mnfr.70466","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T10:12:01Z","timestamp":1776334321000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Isoeugenol Inhibits Growth, Migration, and Invasion in Colorectal Cancer Cells With Distinct Molecular Characteristics"],"prefix":"10.1002","volume":"70","author":[{"given":"Zih\u2010Shuan","family":"Liou","sequence":"first","affiliation":[{"name":"Department of Life Sciences National Central University  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih\u2010Chun","family":"Kuo","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism Department of Internal Medicine Taoyuan Armed Forces General Hospital  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien\u2010Chih","family":"Yeh","sequence":"additional","affiliation":[{"name":"Division of Colon and Rectal Surgery Department of Surgery Taoyuan Armed Forces General Hospital  Taoyuan Taiwan"},{"name":"National Defense Medical Center Tri\u2010Service General Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le Thi Bao","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Life Sciences National Central University  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Qi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Life Sciences National Central University  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li\u2010Jane","family":"Shih","sequence":"additional","affiliation":[{"name":"National Defense Medical Center Tri\u2010Service General Hospital  Taipei Taiwan"},{"name":"Medical Laboratory Taoyuan Armed Forces General Hospital  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih\u2010En","family":"Kao","sequence":"additional","affiliation":[{"name":"Department of Physiology National Cheng Kung University  Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching\u2010Feng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Taipei Tzu Chi Hospital  New Taipei City Taiwan"},{"name":"Institute of Biomedical Sciences Academia Sinica  Taipei Taiwan"},{"name":"Department of Pediatrics Tzu Chi University  Hualien Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung\u2010Hsi","family":"Kao","sequence":"additional","affiliation":[{"name":"Department of Life Sciences National Central University  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui\u2010Chen","family":"Ku","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Taipei Tzu Chi Hospital  New Taipei City Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-327736"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_10_4_1","first-page":"2828","article-title":"TNM and Modified Dukes Staging Along With the Demographic Characteristics of Patients With Colorectal Carcinoma","volume":"7","author":"Akkoca A. 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Molecular Docking Study of Isoeugenol as a Potent Cox and Lox Inhibitor","volume":"9","author":"Zarlaha A.","year":"2014","journal-title":"Digest Journal of Nanomaterials and Biostructures"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.106230"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202100854"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202200872"},{"key":"e_1_2_10_18_1","unstructured":"IARC Working Group on the Identification of Carcinogenic Hazards to Humans Aspartame Methyleugenol and Isoeugenol IARC Monographs on the Identification of Carcinogenic Hazards to Humans134(2024)."},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/392674"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-15-0302"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2005.04.012"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-025-01193-7"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04668-1"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2020.08.016"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2015.08.001"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/15353702221108925"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2019.00107"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201100438"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605846"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers9120171"},{"key":"e_1_2_10_31_1","doi-asserted-by":"crossref","unstructured":"V. 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