{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:59:01Z","timestamp":1791233941652,"version":"4.1.0"},"reference-count":68,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"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-2021R1I1A2060024"],"award-info":[{"award-number":["NRF-2021R1I1A2060024"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Brassinin (BSN), a potent phytoalexin found in cruciferous vegetables, has been found to exhibit diverse anti-neoplastic effects on different cancers. However, the impact of BSN on chronic myelogenous leukemia (CML) cells and the possible mode of its actions have not been described earlier. We investigated the anti-cytotoxic effects of BSN on the KBM5, KCL22, K562, and LAMA84 CML cells and its underlying mechanisms of action in inducing programmed cell death. We noted that BSN could induce apoptosis, autophagy, and paraptosis in CML cells. BSN induced PARP cleavage, subG1 peak increase, and early apoptosis. The potential action of BSN on autophagy activation was confirmed by an LC3 expression and acridine orange assay. In addition, BSN induced paraptosis through increasing the reactive oxygen species (ROS) production, mitochondria damage, and endoplasmic reticulum (ER) stress. Moreover, BSN promoted the activation of the MAPK signaling pathway, and pharmacological inhibitors of this signaling pathway could alleviate all three forms of cell death induced by BSN. Our data indicated that BSN could initiate the activation of apoptosis, autophagy, and paraptosis through modulating the MAPK signaling pathway.<\/jats:p>","DOI":"10.3390\/biology12020307","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T02:01:10Z","timestamp":1676426470000},"page":"307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Brassinin Induces Apoptosis, Autophagy, and Paraptosis via MAPK Signaling Pathway Activation in Chronic Myelogenous Leukemia Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Min Hee","family":"Yang","sequence":"first","affiliation":[{"name":"KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9210-1401","authenticated-orcid":false,"given":"In Jin","family":"Ha","sequence":"additional","affiliation":[{"name":"Korean Medicine Clinical Trial Center (K-CTC), Korean Medicine Hospital, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0060-5777","authenticated-orcid":false,"given":"Seok-Geun","family":"Lee","sequence":"additional","affiliation":[{"name":"Korean Medicine Clinical Trial Center (K-CTC), Korean Medicine Hospital, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6897-2824","authenticated-orcid":false,"given":"Junhee","family":"Lee","sequence":"additional","affiliation":[{"name":"Korean Medicine Clinical Trial Center (K-CTC), Korean Medicine Hospital, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0568-9738","authenticated-orcid":false,"given":"Jae-Young","family":"Um","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautam","family":"Sethi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2882-0612","authenticated-orcid":false,"given":"Kwang Seok","family":"Ahn","sequence":"additional","affiliation":[{"name":"KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4010","DOI":"10.1182\/blood-2003-12-4111","article-title":"The biology of CML blast crisis","volume":"103","author":"Calabretta","year":"2004","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/243290a0","article-title":"Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining","volume":"243","author":"Rowley","year":"1973","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1111\/cbdd.12983","article-title":"Identification of natural inhibitors of Bcr-Abl for the treatment of chronic myeloid leukemia","volume":"90","author":"Parcha","year":"2017","journal-title":"Chem. 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