| RRC ID |
72357
|
| 著者 |
Yano H, Fujiwara Y, Horlad H, Pan C, Kai K, Niino D, Ohsawa K, Higashi M, Nosaka K, Okuno Y, Tamaru JI, Mukasa A, Matsuoka M, Komohara Y.
|
| タイトル |
Blocking cholesterol efflux mechanism is a potential target for antilymphoma therapy.
|
| ジャーナル |
Cancer Sci
|
| Abstract |
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.
|
| 巻・号 |
113(6)
|
| ページ |
2129-2143
|
| 公開日 |
2022-6-1
|
| DOI |
10.1111/cas.15349
|
| PMID |
35343027
|
| PMC |
PMC9207360
|
| MeSH |
ATP-Binding Cassette Transporters* / metabolism
Animals
Cholesterol / metabolism
Cholesterol Esters / metabolism
Foam Cells* / metabolism
Foam Cells* / pathology
Humans
Mice
Scavenger Receptors, Class B / metabolism
|
| IF |
4.966
|
| リソース情報 |
| ヒト・動物細胞 |
ATN-1)RCB1440)
103-LCL(RCB2082)
141‐LCL(RCB2083)
DAUDI(RCB1640)
BALL-1(RCB1882)
TL-1(RCB1871)
RAJI(RCB1647)
SLVL(RCB1702)
HKBML(RCB0820) |
