| 摘要: | Comparative effects of DHA and its peroxidation product 4-HHE on human cancer cells
Background: Fish oil and its constituent, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been known to reduce risk of cardiovascular, inflammatory diseases, to improve brain function and mental health and have anticancer and chemopreventive effects on various types of cancers, such as breast, colon, prostate, endometrium and ovary. In epidemiological studies, fish oil is proven to reduce risk of colon and breast cancer. In this study we tested effects of DHA and its peroxidation product 4-hydroxyhexenal (4-HHE) on colon and breast cancer cells. Lipid peroxidation products may regulate tumourigenesis process and we aimed to compare DHA and 4-HHE’s effects on different types of cancer cells and investigate if DHA’s anticancer effect is due to 4-HHE.
Materials/Methods: Colon (HCT-116 and HT-29) and breast cancer cells (MDAMB-231 and MDAMB-468) were treated with 0, 1, 5, 10, 25 and 50 ?M concentrations of DHA and 4-HHE for 24 and 48 hours and MTT, cell cycle, western blotting assay was performed. For detection of cell signaling pathway, cancer cells were treated for 1 hour with DHA and 4-HHE with the concentrations mentioned above.
Results: Treatment with DHA and 4-HHE decreased cell viability in all cancer cells with dose and time dependently. G2/M arrest was detected in HCT-116 and HT-29 colorectal cancer cells with DHA and 4-HHE treatment. Both treatments induced S phase arrest in MDAMB-231 at 24 hour and G2/M phase at 48 hours. G2/M phase arrest was seen in MDAMB-468 cell line at 48 hour time point. Cell cycle regulatory protein expressions were also modulated with both treatments in all cell lines. P-STAT3 protein expression was reduced with DHA and 4-HHE treatments dose dependently in every cancer cells.
Conclusion: DHA and its peroxidation product 4-HHE decreased cell viability, induced cell cycle arrest, modulated cell cycle regulatory proteins via inhibition of p-STAT3 pathway in human colorectal and breast cancer cells with different patterns. DHA seemed more effective in inhibition of colorectal cancer cells and effect of 4-HHE was superior in human breast cancer cells, especially in MDAMB-231 cells. |
