Exploration of novel metabolic features reflecting statin sensitivity in lung cancer cells

Tashiro, Jiro; Warita, Tomoko; Sugiura, Akihiro; Mizoguchi, Kana; Ishikawa, Takuro; Warita, Katsuhiko

doi:10.51094/jxiv.716

##article.authors##

Tashiro, Jiro Department of Veterinary Anatomy, School of Veterinary Medicine, Tottori university https://orcid.org/0009-0002-6874-0796
Warita, Tomoko Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University
Sugiura, Akihiro Department of Veterinary Anatomy, School of Veterinary Medicine, Tottori University
Mizoguchi, Kana Graduate School of Science and Technology, Kwansei Gakuin University
Ishikawa, Takuro Department of Veterinary Anatomy, School of Veterinary Medicine, Tottori University
Warita, Katsuhiko Department of Veterinary Anatomy, School of Veterinary Medicine, Tottori University

DOI:

https://doi.org/10.51094/jxiv.716

キーワード:

Cancer、 Statin-sensitivity、 CoA、 Cholesterol、 PANK2、 SOAT1

抄録

Statins are cholesterol-lowering drugs often used for the treatment of dyslipidemia. Statins also exert anticancer 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 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 mevalonate pathway flow and CoA content may be limited in statin-sensitive cancer cells. We also suggest that CoA synthesis and cholesterol storage fluctuate with atorvastatin treatment in statin-sensitive cancer cells.

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The authors declare no conflict of interest.

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