2020年7月
Spermine synthesis inhibitor blocks 25-hydroxycholesterol-induced- apoptosis via SREBP2 upregulation in DLD-1 cell spheroids.
Biochemistry and biophysics reports
- ,
- ,
- 巻
- 22
- 号
- 開始ページ
- 100754
- 終了ページ
- 100754
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.bbrep.2020.100754
The oxysterol 25-hydroxycholesterol (25-HC) has diverse physiological activities, including the ability to inhibit anchorage-independent growth of colorectal cancer cells. Here, we found that a polyamine synthesis inhibitor, DFMO, prevented 25-HC-induced apoptosis in non-anchored colorectal cancer DLD-1 cells. Additionally, we found that the spermine synthesis inhibitor APCHA also inhibited 25-HC-induced apoptosis in DLD-1 spheroids. Inhibiting the maturation of SREBP2, a critical regulator of cholesterol synthesis, reversed the effects of APCHA. SREBP2 knockdown also abolished the ability of APCHA to counteract 25-HC activity. Furthermore, APCHA induced SREBP2 maturation and upregulated its transcriptional activity, indicating that altered polyamine metabolism can increase SREBP2 activity and block 25-HC-induced apoptosis in spheroids. These results suggest that crosstalk between polyamine metabolism and cholesterol synthetic pathways via SREBP2 governs the proliferative and malignant properties of colorectal cancer cells.
- リンク情報
- ID情報
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- DOI : 10.1016/j.bbrep.2020.100754
- PubMed ID : 32258442
- PubMed Central 記事ID : PMC7109571