AI Article Synopsis

  • Statins are drugs that lower cholesterol and have anti-cancer effects by inhibiting a key enzyme in cholesterol production.
  • Research shows that the effectiveness of statins varies in different cancer cells, potentially linked to the presence of E-cadherin, which may act as a marker for statin sensitivity.
  • Comparing gene expressions and metabolite levels in lung cancer cell lines revealed that statin-sensitive cells have lower cholesterol synthesis gene expression and reduced levels of related metabolites, indicating that these cells might have a limited capacity for cholesterol production and storage when treated with atorvastatin.

Article Abstract

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.

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Source
http://dx.doi.org/10.1248/bpb.b24-00346DOI Listing

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