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 language | English (US) |
|---|---|
| Journal | Journal of Cellular Physiology |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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Keywords
- carnitine palmitoyltransferase (CPT)
- cellular senescence
- lipidomics
- mitochondrial function
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Cell Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Effects of carnitine palmitoyltransferases on cancer cellular senescence
AU - Guan, Lihuan
AU - Chen, Yixin
AU - Wang, Yongtao
AU - Zhang, Huizhen
AU - Fan, Shicheng
AU - Gao, Yue
AU - Jiao, Tingying
AU - Fu, Kaili
AU - Sun, Jiahong
AU - Yu, Aiming
AU - Huang, Min
AU - Bi, Huichang
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - carnitine palmitoyltransferase (CPT)
KW - cellular senescence
KW - lipidomics
KW - mitochondrial function
UR - http://www.scopus.com/inward/record.url?scp=85052581405&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052581405&partnerID=8YFLogxK
U2 - 10.1002/jcp.27042
DO - 10.1002/jcp.27042
M3 - Article
C2 - 30070697
AN - SCOPUS:85052581405
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
SN - 0021-9541
ER -