# Delta‐9 desaturase reduction in gastrointestinal cells induced to senescence by doxorubicin

## TL;DR

This study shows that doxorubicin-induced cellular senescence reduces Delta-9 desaturase activity, affecting lipid metabolism in pancreatic and hepatic cancer cells.

## Contribution

The novel finding is the consistent downregulation of Delta-9 desaturase in senescent cancer cells, suggesting a potential biomarker for senescence.

## Key findings

- Delta-9 desaturase is downregulated in senescent pancreatic and hepatic cancer cells.
- Senescence reduces the MUFA/SFA ratio in these cells.
- Doxorubicin induces senescence and alters lipid metabolism.

## Abstract

The condition of cellular senescence has specific features, including an altered lipid metabolism. Delta‐9 desaturase (Δ9) catalyzes the conversion of saturated fatty acids, such as palmitic acid and stearic acid, into their monounsaturated forms, palmitoleic and oleic acid, respectively. Δ9 activity is important for most lipid functions, such as membrane fluidity, lipoprotein metabolism and energy storage. The present study aimed to investigate differences in the expression of Δ9 in senescence‐induced pancreatic (MIA‐PaCa‐2 and PANC‐1) and hepatic (Hepa‐RG and HLF) cancer cell lines. Cellular senescence was induced by growing cells in the presence of the chemotherapic drug doxorubicin. Senescence status was determined by the senescence‐associated beta‐galactosidase activity assay kit combined with the p21 and senescence associated secretory phenotype protein assay. Δ9 was downregulated in all senescence‐induced cell lines compared to control cells, in both the lipidomic analysis and when measuring protein levels via western blotting. Hence, our findings demonstrate that the study of membrane lipid composition and the expression levels of Δ9 could potentially form the basis for future applications investigating the state of cellular senescence.

Pancreatic and hepatic cell lines induced to senescence by doxorubicin treatment were used for lipidomic analysis. A downregulation of Δ9 and a reduced MUFA/SFA ratio was found in all senescence‐induced cells compared to untreated control cells.