Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0002329
Title: Saturated fatty acids modulate cell response to DNA damage: Implication for their role in tumorigenesis
Authors: Zeng L. 
Wu G.-Z.
Goh K.J.
Lee Y.M. 
Ng C.C.
You A.B.
Wang J.
Jia D.
Hao A.
Yu Q. 
Li B.
Keywords: actin
DNA
double stranded DNA
doxorubicin
fatty acid synthase
hydroxyurea
myristic acid
palmitic acid
protein Bax
protein p21
protein p53
saturated fatty acid
single stranded DNA
stearic acid
fatty acid
fatty acid synthase
protein p21
protein p53
animal cell
apoptosis
article
cancer cell
carcinogenesis
cell cycle arrest
cell proliferation
cell strain 3T3
cell strain HCT116
cell strain MCF 7
cell transformation
controlled study
DNA damage
DNA strand breakage
embryo
enzyme inhibition
fatty acid synthesis
fibroblast
gene expression regulation
growth inhibition
human
human cell
malignant neoplastic disease
mouse
nonhuman
osteoblast
protein expression
signal transduction
tumor growth
animal
biosynthesis
cell line
drug antagonism
drug effect
fluorescent antibody technique
ionizing radiation
metabolism
phosphorylation
physiology
Western blotting
Murinae
Animals
Blotting, Western
Cell Line
Cell Proliferation
DNA Damage
Doxorubicin
Fatty Acid Synthetase Complex
Fatty Acids
Fluorescent Antibody Technique
Humans
Hydroxyurea
Mice
Oncogene Protein p21(ras)
Osteoblasts
Phosphorylation
Radiation, Ionizing
Tumor Suppressor Protein p53
Issue Date: 2008
Citation: Zeng L., Wu G.-Z., Goh K.J., Lee Y.M., Ng C.C., You A.B., Wang J., Jia D., Hao A., Yu Q., Li B. (2008). Saturated fatty acids modulate cell response to DNA damage: Implication for their role in tumorigenesis. PLoS ONE 3 (6) : e2329. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0002329
Abstract: DNA damage triggers a network of signaling events that leads to cell cycle arrest or apoptosis. This DNA damage response acts as a mechanism to prevent cancer development. It has been reported that fatty acids (FAs) synthesis is increased in many human tumors while inhibition of fatty acid synthase (FASN) could suppress tumor growth. Here we report that saturated fatty acids (SFAs) play a negative role in DNA damage reponse. Palmitic acid, as well as stearic acid and myristic acid, compromised the induction of p21 and Bax expression in response to double stranded breaks and ssDNA, while inhibition or knockdown of FASN enhanced these cellular events. SFAs appeared to regulate p21 and Bax expression via Atr-p53 dependent and independent pathways. These effects were only observed in primary mouse embryonic fibroblasts and osteoblasts, but not in immortalized murine NIH3T3, or transformed HCT116 and MCF-7 cell lines. Accordingly, SFAs showed some positive effects on proliferation of MEFs in response to DNA damage. These results suggest that SFAs, by negatively regulating the DNA damage response pathway, might promote cell transformation, and that increased synthesis of SFAs in precancer/cancer cell might contribute to tumor progression and drug resistance. � 2008 Zeng et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161854
ISSN: 19326203
DOI: 10.1371/journal.pone.0002329
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