Essential fatty acid distribution in the plasma and tissue phospholipids of patients with benign and malignant prostatic disease

Abstract

There is increasing evidence that essential fatty acids (EFA) may have a role to play in the aetiology of some types of cancer although their precise mode of action is unknown. Differences in the metabolism of EFA between patients with benign or malignant prostatic disease may help to elucidate their role in the latter. We have, therefore, measured the concentration of the essential fatty acids, and their metabolites, in the phospholipid fractions of both plasma and tissue, in patients with either benign or malignant prostatic disease. Comparison of the median concentration of fatty acids in each group (n = 10) revealed significant differences between them. The phospholipid component of total lipid was greater in malignant (P less than 0.04, unpaired t-test) than in benign tissue. The concentrations of linoleic acid (LA) and di-homo gamma linolenic acid (DGLA) in plasma and tissue were not different between the two groups of patients, but a significant reduction in arachidonic acid (ARA) (P less than 0.002, Mann-Whitney U-test) and docosapentaenoic acid (DPA) (P = 0.009) concentrations was observed in malignant tissue as compared to benign. Patients with malignant prostatic disease also had a significantly higher concentration of oleic acid in phospholipids from both plasma and prostatic tissue. The stearic to oleic acid ratio was similar in plasma but was significantly reduced in malignant tissue (P = 0.006). We suggest that the decreased arachidonic acid concentration in malignant tissue may be due to its increased metabolism, via the lipoxygenase and cyclooxygenase pathways to produce higher concentrations of eicosanoids, rather than an impairment in desaturase activity in situ.

Prostate cancer and use of nonsteroidal anti-inflammatory drugs: systematic review and meta-analysis

“…Enhanced synthesis of prostaglandins, a consequence of COX-2 upregulation, favours the growth of malignant cells by increasing cell proliferation and inhibiting immune surveillance (Kirschenbaum et al, 2001). Chaudry et al (1991) showed that malignant prostate tissue converts arachidonic acid to PGE 2 at a 10-fold higher rate than benign tissues. In animal studies, several NSAIDs stimulate apoptosis in prostate cancer cells.…”

Induction of cyclo-oxygenase-2 mRNA by prostaglandin E2 in human prostatic carcinoma cells

“…The growth effects of essential fatty acids appear to involve both PGs and leukotrienes (LTs), which interconnect with autocrine regulation through epidermal growth factor-related polypeptides Rose and Connolly, 1992). Moreover, Wahle and coworkers have also shown that human malignant prostatic tissues have significantly reduced AA concentration compared with benign tissue (Chaudry et al, 1991). When these investigators followed the metabolism of labelled AA, significant amounts of the radioactive label was found in PGE2 in both benign and malignant prostatic tissues, with the malignant tissues converting radiolabelled AA to PGE2 at an almost 10-fold higher rate than benign tissues (Chaudry et al, 1994).…”

Inverse association between prostatic polyunsaturated fatty acid and risk of locally advanced prostate carcinoma

“…5,51,52 We previously reported an inverse relation between percent total prostatic PUFA and extraprostatic tumors in 49 men with clinical localized disease. 5 However, differences in individual fatty acids did not reach statistical significance and we did not adjust for other predictors of pathologic stage.…”

“…5 However, differences in individual fatty acids did not reach statistical significance and we did not adjust for other predictors of pathologic stage. Chaudry et al 51 compared prostatic linoleic, dihomogamma-linoleic, and AA levels in 10 men with prostate carcinoma and 10 men with benign prostatic hyperplasia. 51 Levels of docosapentanoic and AA were lower in subjects with prostate carcinoma compared with controls without disease.…”