{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:54:36Z","timestamp":1789019676082,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:00:00Z","timestamp":1727308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kaohsiung Medical University Research Foundation","award":["KMU-Q108022"],"award-info":[{"award-number":["KMU-Q108022"]}]},{"name":"Kaohsiung Medical University Research Foundation","award":["KMU-M109019"],"award-info":[{"award-number":["KMU-M109019"]}]},{"name":"Kaohsiung Medical University Research Foundation","award":["KMU-M111008"],"award-info":[{"award-number":["KMU-M111008"]}]},{"name":"Kaohsiung Medical University Research Foundation","award":["KMU-M112028"],"award-info":[{"award-number":["KMU-M112028"]}]},{"name":"Kaohsiung Medical University Research Foundation","award":["MOST109-2320-B-037-020"],"award-info":[{"award-number":["MOST109-2320-B-037-020"]}]},{"name":"National Science and Technology Council","award":["KMU-Q108022"],"award-info":[{"award-number":["KMU-Q108022"]}]},{"name":"National Science and Technology Council","award":["KMU-M109019"],"award-info":[{"award-number":["KMU-M109019"]}]},{"name":"National Science and Technology Council","award":["KMU-M111008"],"award-info":[{"award-number":["KMU-M111008"]}]},{"name":"National Science and Technology Council","award":["KMU-M112028"],"award-info":[{"award-number":["KMU-M112028"]}]},{"name":"National Science and Technology Council","award":["MOST109-2320-B-037-020"],"award-info":[{"award-number":["MOST109-2320-B-037-020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Glioblastoma multiforme (GBM) is among the most aggressive and challenging brain tumors, with limited treatment options. Cimicifuga\u00a0foetida, a traditional Chinese medicine, has shown promise due to its bioactive components. This study investigates the anti-glioma effects of a methanolic extract of C. foetida (CF-ME) in GBM cell lines. Methods: The effects of CF-ME and its index compounds (caffeic acid, cimifugin, ferulic acid, and isoferulic acid) on GBM cell viability were assessed using MTT assays on U87 MG, A172, and T98G cell lines. The ability of CF-ME to induce cell cycle arrest, apoptosis, and autophagy and inhibit metastasis was evaluated using flow cytometry, Western blotting, and functional assays. Additionally, the synergistic potential of CF-ME with temozolomide (TMZ) was explored. Results: CF-ME significantly reduced GBM cell viability in a dose- and time-dependent manner, induced G1 phase cell cycle arrest, promoted apoptosis via caspase activation, and triggered autophagy. CF-ME also inhibited GBM cell invasion, migration, and adhesion, likely by modulating epithelial\u2013mesenchymal transition (EMT) markers. Combined with TMZ, CF-ME further enhanced reduced GBM cell viability, suggesting a potential synergistic effect. However, the individual index compounds of CF-ME exhibited only modest inhibitory effects, indicating that the full anti-glioma activity may result from the synergistic interactions among its components. Conclusions: CF-ME exhibited potent anti-glioma activity through multiple mechanisms, including cell cycle arrest, apoptosis, autophagy, and the inhibition of metastasis. Combining CF-ME with TMZ further enhanced its therapeutic potential, making it a promising candidate for adjuvant therapy in glioblastoma treatment.<\/jats:p>","DOI":"10.3390\/nu16193254","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T11:40:27Z","timestamp":1727350827000},"page":"3254","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Methanolic Extract of Cimicifuga foetida Induces G1 Cell Cycle Arrest and Apoptosis and Inhibits Metastasis of Glioma Cells"],"prefix":"10.3390","volume":"16","author":[{"given":"Chih-Hsuan","family":"Chang","sequence":"first","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80756, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9170-6268","authenticated-orcid":false,"given":"Hung-Pei","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Hong","family":"Yen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80756, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Ju","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80756, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"key":"ref_1","first-page":"e21822","article-title":"Reclassification of Glioblastoma Multiforme According to the 2021 World Health Organization Classification of Central Nervous System Tumors: A Single Institution Report and Practical Significance","volume":"14","author":"Stoyanov","year":"2022","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1093\/jnen\/64.6.479","article-title":"Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas","volume":"64","author":"Ohgaki","year":"2005","journal-title":"J. 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