Academic Journal
Blocking cholesterol efflux mechanism is a potential target for antilymphoma therapy
| العنوان: | Blocking cholesterol efflux mechanism is a potential target for antilymphoma therapy |
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| المؤلفون: | Yano, Hiromu, Fujiwara, Yukio, Horlad, Hasita, Pan, Chang, Kai, Keitaro, Niino, Daisuke, Ohsawa, Kumiko, Higashi, Morihiro, Nosaka, Kisato, Okuno, Yutaka, Tamaru, Jun‐ichi, Mukasa, Akitake, Matsuoka, Masao, Komohara, Yoshihiro |
| المساهمون: | Japan Society for the Promotion of Science |
| المصدر: | Cancer Science ; volume 113, issue 6, page 2129-2143 ; ISSN 1347-9032 1349-7006 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2022 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Cholesterol is an essential plasma membrane lipid for the maintenance of cellular homeostasis and cancer cell proliferation. Free cholesterol is harmful to cells; therefore, excessive free cholesterol must be quickly esterified by acetyl‐coenzyme A:cholesterol acetyltransferase (ACAT) and exported by scavenger receptor class B member I (SR‐BI) or ATP‐binding cassette protein A1 from specific cells such as macrophage foam cells, which contain cholesteryl ester‐derived 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‐grade 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‐related molecules was significantly upregulated in lymphoma cell lines, with SR‐BI and ACAT inhibitors (BLT‐1 and CI‐976, respectively) impeding lymphoma cell proliferation. Cytoplasmic free cholesterol was increased by ACAT and SR‐BI inhibitors, and the accumulation of free cholesterol induced lymphoma cell apoptosis by inducing endoplasmic reticulum stress. Furthermore, synergistic effects of SR‐BI and ACAT inhibitors were observed in a preclinical study. Treatment with SR‐BI inhibitor suppressed lymphoma progression in a tumor‐bearing mouse model, whereas ACAT inhibitor did not. Therefore, SR‐BI inhibitors are potential new antilymphoma therapeutics that target cholesterol metabolism. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1111/cas.15349 |
| الاتاحة: | http://dx.doi.org/10.1111/cas.15349 https://onlinelibrary.wiley.com/doi/pdf/10.1111/cas.15349 https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.15349 |
| Rights: | http://creativecommons.org/licenses/by-nc/4.0/ |
| رقم الانضمام: | edsbas.BCA95449 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/cas.15349 |
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