{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T11:34:01Z","timestamp":1767008041667,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,10]],"date-time":"2020-10-10T00:00:00Z","timestamp":1602288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 105-2320-B-040-025"],"award-info":[{"award-number":["MOST 105-2320-B-040-025"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cedrus atlantica is widely used in herbal medicine. However, the anti-cancer activity of C. atlantica extract (CAt extract) has not been clarified in hepatocellular carcinoma. In the study, we elucidated the anti-hepatoma capacity of CAt extract on HCC in vitro and in vivo. To explore the anti-hepatoma mechanisms of the CAt extract in vitro, HCC and normal cells were treated with the CAt extract, which showed marked inhibitory effects on HCC cells in a dose-dependent manner; in contrast, the CAt extract treatment was less cytotoxic to normal cells. In addition, our results indicate that the CAt extract induced apoptosis via caspase-dependent and independent apoptosis pathways. Furthermore, the CAt extract inhibited HCC tumor cell growth by restraining cell cycle progression, and it reduced the signaling of the AKT, ERK1\/2, and p38 pathways. In the xenograft model, the CAt extract suppressed HCC tumor cell growth and prolonged lifespan by inhibiting PCNA protein expression, repressing part of the VEGF-induced autocrine pathway, and triggering strong expression of cleaved caspase-3, which contributed to cell apoptosis. Moreover, the CAt extract did not induce any obvious changes in pathological morphology or body weight, suggesting it had no toxicity. CAt extract exerted anti-tumor effects on HCC in vitro and in vivo. Thus, CAt extract could be used as a potential anti-cancer therapeutic agent against HCC.<\/jats:p>","DOI":"10.3390\/molecules25204608","type":"journal-article","created":{"date-parts":[[2020,10,17]],"date-time":"2020-10-17T07:23:22Z","timestamp":1602919402000},"page":"4608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Extract Derived from Cedrus atlantica Acts as an Antitumor Agent on Hepatocellular Carcinoma Growth In Vitro and In Vivo"],"prefix":"10.3390","volume":"25","author":[{"given":"Xiao-Fan","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-1960","authenticated-orcid":false,"given":"Kai-Fu","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6583-1575","authenticated-orcid":false,"given":"Shan-Chih","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1299-3375","authenticated-orcid":false,"given":"Gwo-Tarng","family":"Sheu","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Life and Death, Nanhua University, Chiayi 62249, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7616-6216","authenticated-orcid":false,"given":"Jun-Cheng","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan 33303, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1199-6977","authenticated-orcid":false,"given":"Chih-Yen","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60002, Taiwan"},{"name":"Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2629-1833","authenticated-orcid":false,"given":"Nu-Man","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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