{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:57:22Z","timestamp":1787029042566,"version":"build-2736575974"},"reference-count":32,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2019,10,18]],"date-time":"2019-10-18T00:00:00Z","timestamp":1571356800000},"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":["NRF-2017R1A5A2014768"],"award-info":[{"award-number":["NRF-2017R1A5A2014768"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Chrysanthemum boreale is a plant widespread in East Asia, used in folk medicine to treat various disorders, such as pneumonia, colitis, stomatitis, and carbuncle. Whether the essential oil from C. boreale (ECB) and its active constituents have anti-proliferative activities in lung cancer is unknown. Therefore, we investigated the cytotoxic effects of ECB in A549 and NCI-H358 human lung cancer cells. Culture of A549 and NCI-H358 cells with ECB induced apoptotic cell death, as revealed by an increase in annexin V staining. ECB treatment reduced mitochondrial membrane potential (MMP), disrupted the balance between pro-apoptotic and anti-apoptotic Bcl-2 proteins, and activated caspase-8, -9, and -3, as assessed by western blot analysis. Interestingly, pretreatment with a broad-spectrum caspase inhibitor (z-VAD-fmk) significantly attenuated ECB-induced apoptosis. Furthermore, gas chromatography\u2013mass spectrometry (GC\/MS) analysis of ECB identified six compounds. Among them, \u03b2-caryophyllene exhibited a potent anti-proliferative effect, and thus was identified as the major active compound. \u03b2- Caryophyllene induced G1 cell cycle arrest by downregulating cyclin D1, cyclin E, cyclin-dependent protein kinase (CDK) -2, -4, and -6, and RB phosphorylation, and by upregulating p21CIP1\/WAF1 and p27KIP1. These results indicate that \u03b2-caryophyllene exerts cytotoxic activity in lung cancer cells through induction of cell cycle arrest.<\/jats:p>","DOI":"10.3390\/molecules24203754","type":"journal-article","created":{"date-parts":[[2019,10,18]],"date-time":"2019-10-18T04:12:59Z","timestamp":1571371979000},"page":"3754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["\u03b2-Caryophyllene in the Essential Oil from Chrysanthemum Boreale Induces G1 Phase Cell Cycle Arrest in Human Lung Cancer Cells"],"prefix":"10.3390","volume":"24","author":[{"given":"Kyung-Sook","family":"Chung","sequence":"first","affiliation":[{"name":"College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Young","family":"Hong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"},{"name":"Life and Nanopharmaceutical Science, and Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong-Hun","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"},{"name":"Life and Nanopharmaceutical Science, and Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae-Jun","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"},{"name":"Life and Nanopharmaceutical Science, and Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Yeon","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Hye","family":"Choi","sequence":"additional","affiliation":[{"name":"Life and Nanopharmaceutical Science, and Kyung Hee University, Seoul 02447, Korea"},{"name":"College of Oriental Pharmaceutical Science, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Juhn","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Applied Plant Sciences, Sang-Ji University, Wonju 220-702, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7742-5232","authenticated-orcid":false,"given":"Jongki","family":"Hong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3141-3727","authenticated-orcid":false,"given":"Kyung-Tae","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"},{"name":"Life and Nanopharmaceutical Science, and Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1158\/1055-9965.EPI-19-0221","article-title":"Cancer Progress and Priorities: Lung Cancer","volume":"28","author":"Schabath","year":"2019","journal-title":"Cancer Epidemiol. 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