Differential effects of n-6 and n-3 polyunsaturated fatty acids on cell growth and early gene expression in Swiss 3T3 fibroblasts

✍ Scribed by Ulrich Danesch; Peter C. Weber; Alois Sellmayer

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 869 KB
• Volume: 168
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(199609)168:3<618::aid-jcp14>3.0.co;2-v

✦ Synopsis

Dietary n-3 polyunsaturated fatty acids (PUFAs) have been found to reduce accelerated cell growth. To study the underlying molecular mechanisms, we evaluated the effects of the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) compared with the n-6 PUFA arachidonic acid (AA) on cell growth and early gene mRNA accumulation in Swiss 3T3 fibroblasts. AA significantly increased cell numbers and incorporation of ['HI-thymidine compared with cells treated with EPA and DHA, which did not stimulate cell growth. In contrast to AA and parallel to its effect on cell growth, EPA and DHA did not lead to a pronounced increase in Egr-1 and c-fos mRNA levels. When they were incubated together with AA, both DHA and EPA reduced AA-induced Egr-1 and c-fos mRNA accumulation and incorporation of 'HI-thymidine. We have recently shown that AA strongly increases Egr-1 and c-fos mRNA accumulation in 3T3 fibroblasts through its metabolism to prostaglandin E, (PCE2) and its subsequent activation of protein kinase C (Danesch et al., 1994, J. Biol. Chem., 269:27258-27263). Consistent with the notion that increased PGE, formation is required for the AAinduced early gene mRNA accumulation, EPA and DHA reduced PGE, formation from exogenous ['4C]-AA by more than 60%, but they did not decrease mRNA levels following stimulation with PGE,. We suggest that, in 3T3 fibroblasts, €PA and DHA antagonize AA-induced early gene mRNA accumulation and cell growth by reducing PGE2 formation.