{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T01:57:05Z","timestamp":1781661425011,"version":"3.54.5"},"reference-count":38,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1F1A1069711"],"award-info":[{"award-number":["2020R1F1A1069711"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A2C2088201"],"award-info":[{"award-number":["2019R1A2C2088201"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Colorectal cancer (CRC) is a malignancy of the colon or rectum. It is ranked as the third most common cancer in both men and women worldwide. Early resection permitted by early detection is the best treatment, and chemotherapy is another main treatment, particularly for patients with advanced CRC. A well-known thymidylate synthase (TS) inhibitor, 5-fluorouracil (5-FU), is frequently prescribed to CRC patients; however, drug resistance is a critical limitation of its clinical application. Based on the hypothesis that Coptidis Rhizoma extract (CRE) can abolish this 5-FU resistance, we explored the efficacy and underlying mechanisms of CRE in 5-FU-resistant (HCT116\/R) and parental HCT116 (HCT116\/WT) cells. Compared to treatment with 5-FU alone, combination treatment with CRE and 5-FU drastically reduced the viability of HCT116\/R cells. The cell cycle distribution assay showed significant induction of the G0\/G1 phase arrest by co-treatment with CRE and 5-FU. In addition, the combination of CRE and 5-FU notably suppressed the activity of TS, which was overexpressed in HCT116\/R cells, as compared to HCT116\/WT cells. Our findings support the potential of CRE as an adjuvant agent against 5-FU-resistant colorectal cancers and indicate that the underlying mechanisms might involve inhibition of TS expression.<\/jats:p>","DOI":"10.3390\/molecules26071856","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T14:51:12Z","timestamp":1616683872000},"page":"1856","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase"],"prefix":"10.3390","volume":"26","author":[{"given":"Yong-Hwi","family":"Kang","sequence":"first","affiliation":[{"name":"Institute of Bioscience &amp; Integrative Medicine, Daejeon Oriental Hospital of Daejeon University, Daeduk-daero, Seo-gu, Daejeon 35353, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Bioscience &amp; Integrative Medicine, Daejeon Oriental Hospital of Daejeon University, Daeduk-daero, Seo-gu, Daejeon 35353, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5039-2423","authenticated-orcid":false,"given":"Nam-Hun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Cheonan Oriental Hospital of Daejeon University, 4, Notaesan-ro, Seobuk-gu, Cheonan-si 31099, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Hyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute of Traditional Medicine &amp; Bioscience, Daejeon University, Daehak-ro 62, Dong-gu, Daejeon 34520, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8156-446X","authenticated-orcid":false,"given":"Chang-Seob","family":"Seo","sequence":"additional","affiliation":[{"name":"Research Infrastructure Team, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Gue","family":"Son","sequence":"additional","affiliation":[{"name":"Institute of Bioscience &amp; Integrative Medicine, Daejeon Oriental Hospital of Daejeon University, Daeduk-daero, Seo-gu, Daejeon 35353, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"ref_1","first-page":"394","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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