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  • Saturated fatty acids modulate cell response to DNA damage: implication for their role in tumorigenesis.

Saturated fatty acids modulate cell response to DNA damage: implication for their role in tumorigenesis.

PloS one (2008-06-05)
Li Zeng, Guang-Zhi Wu, Kim Jee Goh, Yew Mun Lee, Chuo Chung Ng, Ang Ben You, Jianhe Wang, Deyong Jia, Aijun Hao, Qiang Yu, Baojie Li
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 response. 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 cells might contribute to tumor progression and drug resistance.

MATERIALS
Product Number
Brand
Product Description

Supelco
Myristic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Myristic acid, analytical standard
Sigma-Aldrich
Myristic acid, natural, ≥98.5%, FG
Sigma-Aldrich
Myristic acid, ≥98.0% (GC)
Sigma-Aldrich
Myristic acid, ≥95%, FCC, FG
Sigma-Aldrich
Myristic acid, Sigma Grade, ≥99%
Sigma-Aldrich
Stearic acid, reagent grade, 95%
Sigma-Aldrich
Stearic acid, Grade I, ≥98.5% (capillary GC)
Sigma-Aldrich
Stearic acid, SAJ first grade, ≥90.0%, powder
Sigma-Aldrich
C75, ≥98% (HPLC), powder
Supelco
Stearic Acid, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Stearic acid, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Supelco
Stearic acid, analytical standard
Sigma-Aldrich
Stearic acid, ≥95%, FCC, FG