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-κB. 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.

The expression of delta 5 desaturase (D5D), delta 6 desaturase (D6D) and delta 9 desaturase (D9D) was determined by RT‐PCR in the human promyelocytic cell line HL60. During 72 h of culture with 10 % FBS, D5D and D6D were upregulated 5 to 6‐fold, whereas D9D approximately doubled. The addition of fatty acids (FAs) to the culture medium suppressed upregulation of all desaturases. N‐3 and n‐6 FA appeared to be more effective than n‐9 or saturated FA. When FAs were added after 72 h, further upregulation during the next 24 h was suppressed for nearly all desaturases and FAs tested, except for D5D when oleic acid (OA) or stearic acid (SA) was added. In cells cultured with restricted amounts of FBS, desaturase expression increased with decreasing concentrations of FBS. Cellular FA content decreased by 60 % in the neutral lipid fraction, whereas that of the phospholipid fraction decreased by 10 % during 72 h of culture. The largest decrease occurred in the sum of n‐3 and n‐6 FA of the neutral lipid fraction, which was reduced by 83 %, whereas the content of these FAs in the phospholipid fraction decreased by 32 %. The results indicate that when the supply of FA to HL60 cells is limited, the intracellular content of n‐3 and n‐6 FA decreases and this leads to upregulation of the desaturases, particularly D5D and D6D. Since HL60 cells resemble human leukocytes, the results suggest that desaturase expression in leukocytes may be exploited as a biomarker for FA status.

Associations between and changes in plasma phospholipid fatty acid (FA) concentrations and expression of delta 5 desaturase (D5D), delta 6 desaturase (D6D) and delta 9 desaturase (D9D) in leucocytes were investigated both before and during n-3 FA supplementation for 2 weeks in 20 healthy individuals. Participants were divided into two groups depending on fish intake: one fish meal or less per week and no marine FA supplement (Lowfish, n = 9) and more than one fish meal per week and/or daily oral marine FA supplement (Highfish, n = 11). Before starting supplementation (t = 0), concentrations of n-3 FAs were significantly lower in the Lowfish group compared to the Highfish group. During supplementation in both groups, n-3 FAs increased, whereas n-6 FAs decreased. D5D expression was significantly higher in Lowfish compared to Highfish at t = 0. No difference in D6D or D9D expression was observed. D5D expression was inversely correlated with EPA, DPA, DHA and total n-3 FA, and positively correlated with the ratio total n-6 FA/total n-3 FA at t = 0. Expression of D5D in the Lowfish group as well as D6D in both groups significantly decreased relative to the expression at t = 0 during the first day of supplement. PUFA concentration was generally predicted by its precursor FA and D5D or D6D expression. The correlations mentioned disappeared after 2 weeks of supplementation. This indicates that steady-state FA desaturase expression is associated with plasma phospholipid FA composition. Whether leucocyte desaturase expression may have potential as a marker of PUFA status merits further investigation.

Cancer cachexia is a complex syndrome marked by involuntary weight and muscle loss, often driven by systemic inflammation. This multicenter, longitudinal observational study investigated circulating microRNA (miRNA) profiles in patients with unresectable locally advanced or metastatic colorectal cancer, comparing those with and without cachexia and inflammation. A total of 168 patients were categorized into four groups based on cachexia and C-reactive protein (CRP) levels. Cachexia was defined using the 2011 consensus criteria, incorporating weight loss, low BMI, and sarcopenia. Patients with both cachexia and systemic inflammation exhibited significantly distinct miRNA profiles as well as poorer overall survival (HR 2.10, p < 0.001) compared to patients with neither condition. No significant differences were observed in patients lacking either cachexia or inflammation or both. Inflammatory cachexia emerged as a biologically distinct entity, with 82 differentially expressed miRNAs. The miR-320-family, miR-6087, miR-4488, miR-29a-3p, miR-194-5p, and miR-10a-5p were most altered, several of which are linked to muscle mass, metabolism, lipid, and protein synthesis. These findings highlight the pivotal role of systemic inflammation in cancer cachexia and support its inclusion in diagnostic criteria. Moreover, circulating miRNAs may serve as promising biomarkers for identifying cachexia in cancer patients.