Selective Growth Suppressive Effect of Pravastatin on Senescent Human Lung Fibroblasts.

Abstract

Various chemical reagents containing inhibitors of mitochondrial activity, antioxidants, nuclear factor-kappa B (NF-kB) inhibitor, mammalian target of rapamycin (mTOR) inhibitor and other clinical therapeutics were screened in order to identify those that selectively decrease the viability of senescent human lung fibroblasts. Cell viability was measured using the CCK-8 assay. The results showed that pravastatin, a drug for hyperlipidemia, decreased the viability of senescent cells but not non-senescent cells. The effect of pravastatin on senescent cells is thought to be due to the inhibition of cell proliferation, rather than cell death. The effect of pravastatin was further investigated using the glucose metabolism assay, which showed that glucose consumption was inhibited both in non-senescent and senescent cells and intracellular nicotinamide adenine dinucleotide (NAD) was decreased in senescent cells. Changes to the mRNA expression levels of senescence-associated genes in response to pravastatin treatment were quantified by real-time-qPCR. There were no significant changes in the relative mRNA expression levels of IL-1β, p16, p21, and p53 in pravastatin-treated non-senescent cells, whereas the expression of IL-1β and p16 were increased by pravastatin only in senescent cells. The results of this study suggest that pravastatin does not induce senolysis, but rather selectively inhibits the proliferation of senescent cells and that cellular senescence is enhanced by decreasing intracellular NAD and promoting IL-1β production.

• Authors: H Ushijima, A Onodera
• Journal: Die Pharmazie (Pharmazie) Vol. 77 Issue 5 Pg. 132-136 (05 01 2022) ISSN: 0031-7144 [Print] Germany
• PMID: 35655385 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• NAD
• Pravastatin

Topics

• Fibroblasts (metabolism)
• Humans
• Lung
• NAD (metabolism, pharmacology)
• Pravastatin (pharmacology)
• RNA, Messenger (metabolism)