{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:21:43Z","timestamp":1790004103789,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,5,5]],"date-time":"2016-05-05T00:00:00Z","timestamp":1462406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["RO1 CA142604"],"award-info":[{"award-number":["RO1 CA142604"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["RO1 CA129347"],"award-info":[{"award-number":["RO1 CA129347"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>The present study is the first to report inhibition of breast cancer cell growth in vitro and in vivo and suppression of self\u2010renewal of breast cancer stem cells (bCSC) by a pine bark component (leelamine). Except for a few recent publications in melanoma, anticancer pharmacology of this interesting phytochemical is largely elusive. Leelamine (LLM) dose\u2010dependently inhibited viability of MDA\u2010MB\u2010231 (triple\u2010negative), MCF\u20107 (estrogen receptor\u2010positive), and SUM159 (triple\u2010negative) human breast cancer cells in association with apoptotic cell death induction. To the contrary, a normal mammary epithelial cell line derived from fibrocystic breast disease and spontaneously immortalized (MCF\u201010A) was fully resistant to LLM\u2010mediated cell growth inhibition and apoptosis induction. LLM also inhibited self\u2010renewal of breast cancer stem cells. Apoptosis induction by LLM in breast cancer cells was accompanied by a modest increase in reactive oxygen species production, which was not due to inhibition of mitochondrial electron transport chain complexes. Nevertheless, ectopic expression of manganese superoxide dismutase conferred partial protection against LLM\u2010induced cell death but only at a lower yet pharmacologically relevant concentration. Exposure of breast cancer cells to LLM resulted in (a) induction and\/or activation of multidomain proapoptotic proteins Bax and Bak, (b) caspase\u20109 activation, and (c) cytosolic release of cytochrome <jats:italic>c<\/jats:italic>. Bax and Bak deficiency in immortalized fibroblasts conferred significant protection against cell death by LLM. Intraperitoneal administration of LLM (7.5\u2009mg\/kg; 5\u2009times\/wk) suppressed the growth of orthotopic SUM159 xenografts in mice without any toxicity. In conclusion, the present study provides critical preclinical data to warrant further investigation of LLM. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22497","type":"journal-article","created":{"date-parts":[[2016,5,5]],"date-time":"2016-05-05T15:22:55Z","timestamp":1462461775000},"page":"337-348","source":"Crossref","is-referenced-by-count":23,"title":["Cancer\u2010selective death of human breast cancer cells by leelamine is mediated by bax and bak activation"],"prefix":"10.1002","volume":"56","author":[{"given":"Anuradha","family":"Sehrawat","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute University of Pittsburgh School of Medicine Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su\u2010Hyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, University of 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