Effects of carnitine palmitoyltransferases on cancer cellular senescence

This study revealed that carnitine palmitoyltransferase 1C (CPT1C) knockdown exhibited the strongest impact on cell growth arrest and senescence, lipid change and accumulation, and mitochondrial dysfunction among all members of the CPT family. In addition, only knocking down CPT1C could downregulate the protein expression of c ‐Myc and cyclin D1 and upregulate the cell cycle inhibitor p27 significantly, which contributes to the potential molecular mechanism of CPT1C knockdown‐induced cellular senescence. The carnitine palmitoyltransferase (CPT) family is essential for fatty acid oxidation. Recently, we found that CPT1C, one of the CPT1 isoforms, plays a vital role in cancer cellular senescence. However, it is unclear whether other isoforms (CPT1A, CPT1B, and CPT2) have the same effect on cellular senescence. This study illustrates the different effects of CPT knockdown on PANC ‐1 cell proliferation and senescence and MDA‐MB‐231 cell proliferation and senescence, as demonstrated by cell cycle kinetics, Bromodeoxyuridine incorporation, senescence‐associated β‐galactosidase activity, colony formation, and messenger RNA (mRNA) expression of key senescence‐associa ted secretory phenotype factors. CPT1C exhibits the most substantial effect on cell senescence. Lipidomics analysis was performed to further reveal that the knockdown of CPTs changed the contents of lipids involved in mitochondrial function, and lipid accumulation was induced. Moreover, the differen t ef...
Source: Journal of Cellular Physiology - Category: Cytology Authors: Tags: ORIGINAL RESEARCH ARTICLE Source Type: research