Metabolic Flux Analysis Reveals the Roles of Stearate and Oleate on CPT1C-mediated Tumor Cell Senescence

Cellular senescence is a state of proliferative arrest, and the development of carcinoma can be suppressed by conferring tumor cell senescence. Recently, we found that carnitine palmitoyltransferase 1C (CPT1C) controls tumor cell proliferation and senescence via regulating lipid metabolism and mitochondrial function. Here, 13C-metabolic flux analysis (13C-MFA) was performed and the results revealed that CPT1C knockdown in MDA-MB-231 cells significantly induced cellular senescence accompanied by altered fatty acid metabolism. Strikingly, stearate synthesis was decreased while oleate was increased. Furthermore, stearate significantly inhibited proliferation while oleate reversed the senescent phenotype induced by silencing CPT1C in MDA-MB-231 cells as well as PANC-1 cells. A939572, an inhibitor of stearoyl-Coenzyme A desaturase 1, had the same effect as stearate to inhibit cellular proliferation. These results demonstrated that stearate and oleate are involved in CPT1C-mediated tumor cellular senescence, and the regulation of stearate/oleate rate via inhibition of SCD-1 could be an additional strategy with depletion of CPT1C for cancer therapy.

 

Comments:

The passage you provided describes a study that investigated the role of carnitine palmitoyltransferase 1C (CPT1C) in controlling tumor cell proliferation and senescence through the regulation of lipid metabolism and mitochondrial function. The researchers performed 13C-metabolic flux analysis (13C-MFA) and observed that knocking down CPT1C in MDA-MB-231 cells led to cellular senescence and altered fatty acid metabolism.

Specifically, the study found that the synthesis of stearate, a type of fatty acid, was decreased, while the synthesis of oleate, another type of fatty acid, was increased upon CPT1C knockdown. Additionally, they discovered that stearate had an inhibitory effect on cell proliferation, while oleate reversed the senescent phenotype induced by silencing CPT1C in MDA-MB-231 and PANC-1 cells.

Furthermore, the researchers used A939572, an inhibitor of stearoyl-Coenzyme A desaturase 1 (SCD-1), and found that it had a similar effect as stearate in inhibiting cellular proliferation. This suggests that the regulation of the stearate/oleate ratio, potentially through inhibition of SCD-1, could be an additional strategy for cancer therapy in combination with depleting CPT1C.

In summary, the study suggests that CPT1C plays a role in tumor cell proliferation and senescence by controlling lipid metabolism and mitochondrial function. It highlights the involvement of stearate and oleate in this process and proposes that modulating the stearate/oleate ratio, possibly through inhibition of SCD-1, could be a potential therapeutic approach in cancer treatment when combined with CPT1C depletion.

Related Products

Cat.No.	Product Name	Information
S9607	A939572	A939572 is a potent and orally bioavailable stearoyl-CoA desaturase1 (SCD1) inhibitor with IC50 of <4 nM and 37 nM for mSCD1 and hSCD1, respectively.

Related Targets

SCD