Effects of carnitine palmitoyltransferases on cancer cellular senescence

Lihuan Guan, Yixin Chen, Yongtao Wang, Huizhen Zhang, Shicheng Fan, Yue Gao, Tingying Jiao, Kaili Fu, Jiahong Sun, Aiming Yu, Min Huang, Huichang Bi

Research output: Contribution to journalArticle

Abstract

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-associated 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 different effects of the isoform deficiencies on mitochondrial function were measured and compared by the level of radical oxygen species, mitochondrial transmembrane potential, and the respiratory capacity, and the expression of the genes involved in mitochondrial function were determined at the mRNA level. In summary, CPT1C exerts the most significant effect on mitochondrial dysfunction-associated tumor cellular senescence among the members of the CPT family, which further supports the crucial role of CPT1C in cellular senescence and suggests that inhibition of CPT1C may represent as a new strategy for cancer treatment through the induction of tumor senescence.

Original languageEnglish (US)
JournalJournal of Cellular Physiology
DOIs
StateAccepted/In press - Jan 1 2018

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Carnitine O-Palmitoyltransferase
Cell Aging
Protein Isoforms
Cell proliferation
Tumors
Galactosidases
Lipids
Neoplasms
Messenger RNA
Essential Fatty Acids
Oncology
Bromodeoxyuridine
Reactive Oxygen Species
Genes
Cells
Cell Proliferation
Oxidation
Kinetics
Membrane Potentials
Cell Cycle

Keywords

  • carnitine palmitoyltransferase (CPT)
  • cellular senescence
  • lipidomics
  • mitochondrial function

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Guan, L., Chen, Y., Wang, Y., Zhang, H., Fan, S., Gao, Y., ... Bi, H. (Accepted/In press). Effects of carnitine palmitoyltransferases on cancer cellular senescence. Journal of Cellular Physiology. https://doi.org/10.1002/jcp.27042

Effects of carnitine palmitoyltransferases on cancer cellular senescence. / Guan, Lihuan; Chen, Yixin; Wang, Yongtao; Zhang, Huizhen; Fan, Shicheng; Gao, Yue; Jiao, Tingying; Fu, Kaili; Sun, Jiahong; Yu, Aiming; Huang, Min; Bi, Huichang.

In: Journal of Cellular Physiology, 01.01.2018.

Research output: Contribution to journalArticle

Guan, L, Chen, Y, Wang, Y, Zhang, H, Fan, S, Gao, Y, Jiao, T, Fu, K, Sun, J, Yu, A, Huang, M & Bi, H 2018, 'Effects of carnitine palmitoyltransferases on cancer cellular senescence', Journal of Cellular Physiology. https://doi.org/10.1002/jcp.27042
Guan, Lihuan ; Chen, Yixin ; Wang, Yongtao ; Zhang, Huizhen ; Fan, Shicheng ; Gao, Yue ; Jiao, Tingying ; Fu, Kaili ; Sun, Jiahong ; Yu, Aiming ; Huang, Min ; Bi, Huichang. / Effects of carnitine palmitoyltransferases on cancer cellular senescence. In: Journal of Cellular Physiology. 2018.
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