{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:08:06Z","timestamp":1788872886390,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1A2C2003277"],"award-info":[{"award-number":["2021R1A2C2003277"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Though\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Rhus verniciflua<\/jats:italic>\n                    <\/jats:styled-content>\n                    and\n                    <jats:italic>Artemisia capillaris<\/jats:italic>\n                    have been traditionally prescribed for liver ailments, the molecular antitumor mechanism of their ethanol extract (RHART) remains undefined in hepatocellular carcinoma (HCC). Thus, this study aimed to elucidate the apoptotic mechanisms of RHART, focusing on its regulation of oncogenic drivers\u2014cleavage and polyadenylation specificity factor 6 (CPSF6), monocarboxylate transporter 4 (MCT4), and c\u2010Myc\u2014and glycolysis\u2010related pathways. RHART quality was standardized by HPLC fingerprinting. Cytotoxicity, apoptosis, and protein expression were analyzed using MTT, cell cycle, and Western blot assays in RHART\u2010treated Hep3B and Huh7 cells. Functional rescue assays were conducted by overexpressing CPSF6 or c\u2010Myc, while CPSF6\u2013MCT4 interaction was confirmed by immunoprecipitation. The in\u00a0vivo efficacy of RHART was validated using Hep3B xenografts in BALB\/c nude mice followed by immunohistochemistry. RHART treatment induced pronounced cytotoxicity and apoptosis, as indicated by an elevated sub\u2010G1 population and cleavage of PARP and caspase\u20103. RHART markedly downregulated CPSF6, MCT4, c\u2010Myc, and glycolytic enzymes (HK2, PKM2, LDHA), thereby reducing glucose utilization and lactate output. CPSF6 directly interacted with MCT4, and overexpression of CPSF6 or c\u2010Myc counteracted the capacity of RHART to induce apoptosis and metabolic reprogramming. In\u00a0vivo, RHART significantly suppressed tumor growth and expression of CPSF6, MCT4, PCNA, and PKM2, while enhancing cleaved caspase\u20103. These findings provide scientific evidence that RHART induces apoptotic and metabolic reprogramming effects in hepatocellular carcinoma by targeting the CPSF6\/MCT4\/c\u2010Myc signaling axis, underscoring its potential as a novel natural therapeutic candidate for liver cancer.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70284","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T04:09:56Z","timestamp":1771474196000},"page":"2556-2568","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Apoptosis and Metabolic Reprogramming by\n                    <scp>RHART<\/scp>\n                    in Hepatocellular Carcinoma Through the\n                    <scp>CPSF6<\/scp>\n                    \/\n                    <scp>MCT4<\/scp>\n                    \/c\u2010Myc Signaling In\u00a0Vitro and In\u00a0Vivo"],"prefix":"10.1002","volume":"40","author":[{"given":"Youngsang","family":"Park","sequence":"first","affiliation":[{"name":"College of Korean Medicine, Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su\u2010Yeon","family":"Park","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8678-156X","authenticated-orcid":false,"given":"Bonglee","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bum\u2010Sang","family":"Shim","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Seok","family":"Joh","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5285-9138","authenticated-orcid":false,"given":"Ki Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung\u2010Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010020\u20100530\u20104"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.06.023"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118009"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.04.017"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/874276"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.009093"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5546446"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201009\u20100889"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/7512159"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0312939"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28202"},{"issue":"4","key":"e_1_2_13_13_1","first-page":"435","article-title":"The c\u2010Myc Oncogene in Tumor Progression","volume":"4","author":"Garte S. 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