DHA Alters Expression of Target Proteins of Cancer Therapy in Chemotherapy Resistant SW620 Colon Cancer Cells

Abstract

Diets rich in n-3 polyunsaturated fatty acids (PUFAs) have been associated with a reduced risk of several types of cancer. Recent reports have suggested that these PUFAs enhance the cytotoxic effect of cancer chemoradiotherapy. The effect of docosahexaenoic acid (DHA) on key cell cycle regulators and target proteins of cancer therapy was investigated in the human malign colon cancer cell line SW620. Cell cycle check point proteins such as p21 and stratifin (14-3-3 sigma) increased at mRNA and protein level, whereas cell cycle progression proteins such as cell division cycle 25 homolog and cyclin-dependent kinase 1 decreased after DHA treatment. Protein levels of inhibitors of apoptosis family members associated with chemotherapy resistance and cancer malignancy, survivin and livin, decreased after the same treatment: likewise the expression of NF-kappaB. Levels of the proapoptotic proteins phosphorylated p38 MAPK and growth arrest-inducible and DNA damage-inducible gene 153/C/EBP-homologous protein (CHOP) increased. The results indicate that DHA treatment causes simultaneous cell cycle arrest in both the G1 and G2 phase. In conclusion, DHA affects several target proteins of chemotherapy in a favorable way. This may explain the observed enhanced chemosensitivity in cancer cells supplemented with n-3 PUFAs and encourage further studies investigating the role of n-3 PUFAs as adjuvant to chemotherapy and radiotherapy in vivo.

Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

“…It is thought that hypermethylation at CpG islands at the gene promoter of the 14-3-3 sigma causes the downregulation of the protein in breast cancer patients (19). It was recently determined that docosahexaenoic acid increased the amount of 14-3-3 sigma protein expressed in colon cancer cells (41). Collectively, these data raise the possibility that n-3 fatty acids may upregulate 14-3-3 sigma through an epigenetic mechanism.…”

Docosahexaenoic fatty acid (DHA) in the regulation of colon cell growth and cell death: A review

“…Several key transcripts involved in the regulation of both the G1 and G2 phases of the cell cycle were affected by DHA treatment in the SW620 cell line derived from lymph node metastasis of colon cancer. Generally, molecules involved in cell cycle progression, such as Cdc25c, Cdc25b, Cdc20, CDK1, CDK2, and cyclin D, A, and B, were down-regulated, whereas molecules involved in cell cycle arrest such as p21 and stratifin were up-regulated 77 . SW620 cells and cell line SW480, derived from primary tumour of the same patient, accumulated DHA differently in TGs and/or cholesterol ester-enriched lipid droplets.…”

“…High XIAP expression correlates with poor clinical outcome, resistance to chemotherapy and radiotherapy in different colon cancer cell lines 71 . DHA was shown to down-regulate mRNA as well as the protein level of two other inhibitors of apoptosis, survivin and livin, in cancer cells 77 . Further, the immediate and dramatic down-regulation of FLIP, a potent inhibitor of caspase-8 activation, appears to be a significant event in the induction of apoptosis in colon cancer cells after DHA and EPA supplementation 71 .…”

Preparation of coffee oil-algae oil-based nanoemulsions and the study of their inhibition effect on UVA-induced skin damage in mice and melanoma cell growth

“…58 In a later study dealing with the effect of DHA standard (0-200 µM) on the inhibition of liver cancer cells MHCC97L, the expressions of CDK2, cyclin E, and cyclin A showed a dose-dependent decrease, but the cell cycle was arrested at sub-G1 phase. 44 Interestingly, in another study, Slagsvold et al 59 illustrated that the cell cycle of colon cancer cells SW620 was arrested at G1 and G2 phases after treatment with DHA standard …”