| Autor: |
Tashiro J; Department of Veterinary Anatomy, School of Veterinary Medicine, Tottori University., Warita T; Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University., Sugiura A; Department of Veterinary Anatomy, School of Veterinary Medicine, Tottori University., Mizoguchi K; Graduate School of Science and Technology, Kwansei Gakuin University., Ishikawa T; Department of Veterinary Anatomy, School of Veterinary Medicine, Tottori University., Warita K; Department of Veterinary Anatomy, School of Veterinary Medicine, Tottori University. |
| Jazyk: |
angličtina |
| Zdroj: |
Biological & pharmaceutical bulletin [Biol Pharm Bull] 2024; Vol. 47 (12), pp. 1992-2002. |
| DOI: |
10.1248/bpb.b24-00346 |
| Abstrakt: |
Statins are cholesterol-lowering drugs often used for the treatment of dyslipidemia. Statins also exert anti-cancer effects by inhibiting hydroxymethylglutaryl-CoA reductase (HMGCR), a rate-limiting enzyme in cholesterol synthesis. We previously reported that the susceptibility to statin treatment differs among cancer cells and that functional E-cadherin expression on the plasma membrane could be a biomarker of statin sensitivity in cancer cells. However, the detailed qualitative and molecular differences between statin-sensitive and statin-resistant cancer cells remain unclear. Here, we explored novel parameters related to statin sensitivity by comparing gene expression profiles and metabolite contents between statin-sensitive and statin-resistant lung cancer cell lines. We found that the expression of most cholesterol synthesis genes was lower in the statin-sensitive cancer cell line, HOP-92, than in the statin-resistant cancer cell line, NCI-H322M. Moreover, HOP-92 cells originally exhibited lower levels of CoA and HMG-CoA. Additionally, atorvastatin decreased the mRNA expression of PANK2, a rate-limiting enzyme in CoA synthesis. Atorvastatin also reduced the mRNA levels of the cholesterol esterification enzyme SOAT1, which was consistent with a decrease in the ratio of cholesterol ester to total cholesterol in HOP-92 cells. Our data suggest that the cholesterol synthetic flow and CoA content may be limited in statin-sensitive cancer cells. We also suggest that CoA synthesis and cholesterol storage may fluctuate with atorvastatin treatment in statin-sensitive cancer cells. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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