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Free cholesterol is harmful to cells; therefore, excessive free cholesterol must be quickly esterified by acetyl\u2010coenzyme A:cholesterol acetyltransferase (ACAT) and exported by scavenger receptor class B member I (SR\u2010BI) or ATP\u2010binding cassette protein A1 from specific cells such as macrophage foam cells, which contain cholesteryl ester\u2010derived vacuoles. Many vacuoles are present in the cytoplasm of Burkitt lymphoma cells. In this study, we observed that these vacuoles are often seen in high\u2010grade lymphomas. Cell culture study using lymphoma cell lines found that esterified cholesterol is the main component of these vacuoles and the expression of cholesterol metabolism\u2010related molecules was significantly upregulated in lymphoma cell lines, with SR\u2010BI and ACAT inhibitors (BLT\u20101 and CI\u2010976, respectively) impeding lymphoma cell proliferation. Cytoplasmic free cholesterol was increased by ACAT and SR\u2010BI inhibitors, and the accumulation of free cholesterol induced lymphoma cell apoptosis by inducing endoplasmic reticulum stress. Furthermore, synergistic effects of SR\u2010BI and ACAT inhibitors were observed in a preclinical study. Treatment with SR\u2010BI inhibitor suppressed lymphoma progression in a tumor\u2010bearing mouse model, whereas ACAT inhibitor did not. Therefore, SR\u2010BI inhibitors are potential new antilymphoma therapeutics that target cholesterol metabolism.<\/jats:p>","DOI":"10.1111\/cas.15349","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T07:35:37Z","timestamp":1648452937000},"page":"2129-2143","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Blocking cholesterol efflux mechanism is a potential target for antilymphoma therapy"],"prefix":"10.1111","volume":"113","author":[{"given":"Hiromu","family":"Yano","sequence":"first","affiliation":[{"name":"Department of Cell Pathology Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2074-0597","authenticated-orcid":false,"given":"Yukio","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Cell Pathology Graduate School of Medical 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