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18:1 n7 fatty acids inhibit growth and decrease inositol phosphate release in HT-29 cells compared to n9 fatty acids
A B Awad1, T Herrmann, C S Fink
1Nutrition Program, State University of New York at Buffalo 14214, USA.
Abstract:
Studies have shown that trans fatty acids may play a role in the development of chronic diseases such as heart disease and cancer. The objective of the present project was to examine the effect of supplementation with 18:1 isomers, both positional and geometrical, as compared to 18:0 on the growth, membrane fatty acid composition and the phosphoinositide cycle of HT-29 human colon cancer cells. Cells were supplemented with 30 microM stearic acid (18:0), elaidic acid (18:1, n9, trans), oleic acid (18:1, n9, cis), vaccenic acid (18:1, n7, cis) or trans-vaccenic acid (18:1, n7, trans) as sodium salts complexed to fatty acid-free bovine serum. Cells were grown in these media for 9 days. Cell growth was examined by counting the number of cells and expressed as percentage of control (18:0 supplemented cells). The phosphoinositide (PI) cycle was examined by measuring the inositol phosphate (IP) released from phosphoinositides in the absence (basal) or presence of stimuli (0.1 mM carbachol, 0.1 mM A23187 or 20 mM NaF). The results obtained indicated that cis and trans n7 fatty acids inhibited the growth of HT-29 cells by 11% and 23%, respectively, as compared to 18:0 supplementation. 18:1, n9 had no effect on tumor growth. Supplementation with all forms of 18:1 resulted in an increase in IP and IP2 production as compared to 18:0 supplemented cells without influencing IP3. The presence of the double bond at the 9 position in the supplemented fatty acid increases total IP production by 59% and in the cis form by 37% above the control. The breakdown of phosphoinositides in the absence and presence of several stimuli supports the observed finding on IP. Trans fatty acid supplementation resulted in lower hydrolysis of PI as compared to cis fatty acids. It is concluded that the observed inhibition of tumor growth by the vaccenic acids may be mediated by their effect(s) on the PI cycle which may be associated with their incorporation into membrane lipids.
Insights
Trans and cis vaccenic acids (18:1, n7) inhibited colon cancer cell growth, while 18:1, n9 isomers had no effect. Vaccenic acids impacted the phosphoinositide cycle, suggesting a mechanism for growth inhibition.
Area of Science:
- Cell Biology
- Biochemistry
- Cancer Research
Background:
- Trans fatty acids are implicated in chronic diseases, including cancer.
- Understanding the specific effects of different fatty acid isomers on cancer cells is crucial for targeted interventions.
- The phosphoinositide cycle plays a role in cellular signaling and proliferation.
Purpose of the Study:
- To investigate the impact of various 18:1 fatty acid isomers (positional and geometrical) compared to 18:0 on HT-29 human colon cancer cell growth.
- To analyze the effects of these fatty acids on the phosphoinositide cycle in colon cancer cells.
- To explore potential mechanisms linking fatty acid supplementation to cancer cell behavior.
Main Methods:
- HT-29 cells were supplemented with stearic acid (18:0), elaidic acid (18:1, n9, trans), oleic acid (18:1, n9, cis), vaccenic acid (18:1, n7, cis), or trans-vaccenic acid (18:1, n7, trans).
- Cell growth was quantified by cell counting over a 9-day period.
- The phosphoinositide cycle was assessed by measuring inositol phosphate production under basal and stimulated conditions.
Main Results:
- Cis and trans n7 fatty acids (vaccenic acids) inhibited HT-29 cell growth by 11% and 23%, respectively, compared to the control (18:0).
- 18:1, n9 isomers (elaidic and oleic acids) did not affect tumor growth.
- All 18:1 isomers increased inositol phosphate (IP) and IP2 production, with a notable increase in total IP production for 18:1, n9 isomers. Trans fatty acid supplementation led to lower phosphoinositide hydrolysis than cis forms.
Conclusions:
- Vaccenic acids (cis and trans 18:1, n7) exhibit inhibitory effects on human colon cancer cell growth.
- The observed growth inhibition may be mediated by alterations in the phosphoinositide cycle.
- Incorporation of vaccenic acids into membrane lipids could influence their anti-cancer effects.