Marine fatty acids and cancer

Department of Clinical and Molecular Medicine

Marine fatty acids and cancer

Marine fatty acids and cancer

Fatty fish and plant-based foods, such as seeds, oils and nuts, are important sources of omega-3 fatty acids (n-3 FAs). Numerous studies indicate an inverse relationship between dietary intake of n-3 polyunsaturated fatty acids (PUFAs) and breast, prostate and colon cancer.

Animal and cell culture studies show that n-3 PUFAs inhibit cell proliferation and induce programmed cell death (apoptosis). However, the molecular mechanisms behind these effects are complex and unclear. Identifying these mechanisms is important for PUFAs' potential impact on cancer therapy as well as cancer prevention.

The project investigates signalling pathways involved in PUFA-induced growth arrest/apoptosis in human cancer cells in vitro and in vivo. We use RNA-isolation, gene expression profiling, RT-PCR, immunoblot analysis, lipid analysis, flow cytometry, calcium measurements, siRNA technology, exome sequencing and proliferation assays.

Reserch results

N-3 PUFAs causes extensive changes in gene expression patterns at mRNA level in human cancer cell lines. Early changes include ER stress and unfolded protein response (UPR), followed by growth arrest in several cancer cell lines treated with DHA or EPA. Key mediators of ER stress and UPR like eIF2a -P, ATF4, TRIB3, CHOP and SQSTM-1 (p62) were found induced at protein level after DHA treatment. ER-stress may coordinate many of the downstream changes observed like calcium homeostasis, lipid metabolism and cell cycle arrest. The sensitivity towards DHA correlates with the basal level of autophagy and MAP1C3B-II in colorectal cancer cell lines.

Ongoing work

Study the importance of ER stress and UPR signalling on cytostatic and cytotoxic effect of PUFAs in human cancer cells, and explore the link between PUFA-induced activation of UPR and autophagy. Study the correlation between n-3 PUFA sensitivity and autophagy level, gene expression and single nucleotide variants in genes.

07 Jun 2018