{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:36:44Z","timestamp":1785418604616,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NIGMS 1SC1GM121202"],"award-info":[{"award-number":["NIGMS 1SC1GM121202"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1R35GM149318"],"award-info":[{"award-number":["1R35GM149318"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NIMHD U54MD007598"],"award-info":[{"award-number":["NIMHD U54MD007598"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["NIGMS 1SC1GM121202"],"award-info":[{"award-number":["NIGMS 1SC1GM121202"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1R35GM149318"],"award-info":[{"award-number":["1R35GM149318"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NIMHD U54MD007598"],"award-info":[{"award-number":["NIMHD U54MD007598"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Arctigenin (Arc), a novel anti-inflammatory lignan derived primarily from Arctium lappa, has demonstrated promising anticancer activity in multiple cancer types. This study was designed to evaluate the anticancer efficacy of Arc across distinct molecular subtypes of breast cancer in vitro and in vivo and to gain mechanistic insights into its mode of action. In vitro evaluation was conducted in estrogen-receptor-positive MCF-7, human epidermal growth factor receptor 2 (HER2)-positive SKBR3, and triple-negative MDA-MB-231 breast cancer cell lines. In vivo efficacy and safety were evaluated using female severe combined immunodeficient (SCID) mice (5\u20137 weeks old) bearing MCF-7 or MDA-MB-231 xenografts. Mice received daily oral gavage of Arc at 50 mg\/kg body weight for 8 weeks. In vitro, Arc inhibited cell proliferation across all three breast cancer subtypes in a dose-dependent manner. PCR-array analysis of gene expression revealed that Arc targets multiple signaling molecules involved in cell proliferation, cell cycle regulation, apoptosis, migration\/invasion, and drug transport, demonstrating a subtype-specific target profile. Arc induced cell-cycle arrest at the G2\/M phase in MCF-7 cells and at G0\/G1 in MDA-MB-231 cells, accompanied by significant induction of apoptosis in both cell lines. Migration assays further demonstrated marked inhibition of wound closure in Arc-treated cells. In vivo, Arc treatment significantly inhibited tumor growth in both xenograft models, decreased Ki67 expression, and produced no overt toxicity. In summary, Arc exhibits potent anticancer activity against distinct breast cancer subtypes through multi-targeting mechanisms. Given the heterogeneity of breast cancer, Arc appears to be a promising candidate for further preclinical investigation.<\/jats:p>","DOI":"10.3390\/ijms27115055","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:46:48Z","timestamp":1780494408000},"page":"5055","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Arctigenin Suppresses Breast Cancer Growth In Vitro and In Vivo Through Subtype-Specific Multi-Targeting Activity"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5900-1644","authenticated-orcid":false,"given":"Joshua","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA"},{"name":"Institute for Advanced Biomedical Research, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4720-767X","authenticated-orcid":false,"given":"Qiongyu","family":"Hao","sequence":"additional","affiliation":[{"name":"Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA"},{"name":"Institute for Advanced Biomedical Research, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7195-9601","authenticated-orcid":false,"given":"Ke","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA"},{"name":"Institute for Advanced Biomedical Research, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahya","family":"Elshimali","sequence":"additional","affiliation":[{"name":"Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA"},{"name":"Institute for Advanced Biomedical Research, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3159-6436","authenticated-orcid":false,"given":"Ali","family":"Andalibi","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biomedical Research, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cancer Research and Training, Charles R. 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