Arachidonic acid metabolism in benign and malignant prostatic tissue in vitro: Effects of fatty acids and cyclooxygenase inhibitors

Abstract

Concentrations of fatty acids (FA) in prostatic tissue of patients with either benign or malignant prostatic disease have previously been shown to be significantly different. In particular, there was a significant reduction in arachidonic acid (AA, C20:4n-6) and docosapentaenoic acid (DPA, C22:5n-6) concentrations in malignant prostatic tissue (PCa) phospholipids (PL). It was suggested that the decreased AA concentration in PCa may be due to its increased metabolism via the cyclooxygenase (CO) and/or lipoxygenase (LO) pathways to produce eicosanoids such as prostaglandins (PGs) and/or leukotrienes (LTs) rather than an impairment in desaturase activity in situ. The eicosanoid production in benign prostatic tissue (BPH) and PCa was determined using [3H]AA. The only eicosanoid produced in significant amounts by either tissue was PGE2 and PCa converted radiolabelled AA to PGE2 at an almost 10-fold higher rate than BPH. PGE2 production from [3H]AA by PCa was investigated in the presence of oleic acid (OA, C18:1n-9), eicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA, C22:6n-3), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosatetraynoic acid (ETYA) and ketoprofen (KPN) respectively. OA was found to be the most effective inhibitor of PGE2 production by PCa compared with DHA, EPA, ETYA and KPN, while DGLA was the least effective. Diacylglycerol (DAG) formation from labelled AA by PCa was about 4-fold greater than in BPH. Such high levels of DAG may be a means of promoting tumorigenesis through activation of protein kinase C as found with phorbol esters which can be regarded as DAG analogues.

Metabolic alterations in urine extracellular vesicles are associated to prostate cancer pathogenesis and progression

“…Interestingly, it has been also reported that arachidonic acid level is lower in prostatic tissue from PCa patients [35]. In agreement with the reduction of the substrate arachidonic acid in PCa, it has been found that the level of their products (12-and 20-HETE, and PGE2) are higher in the tissue [36,37] and also in urine [38]. These studies along with many others have already shown that the metabolism of arachidonic acid and their products plays an important role in PCa development, and in fact, represents an important therapeutics target (reviewed in [39]).…”

15-Lipoxygenase-2 (15-LOX-2) Is Expressed in Benign Prostatic Epithelium and Reduced in Prostate Adenocarcinoma

“…In addition to formation of large amounts of 15-HETE on incubation of this prostate tissue with AA, by immunohistochemistry, the anti-15-LOX-2 antibody uniformly stained benign prostate epithelium but did not stain the Few studies have examined the possible significance of AA metabolism or the presence of cyclooxygenase or lipoxygenase enzymes in benign prostate and prostatic neoplasia. Chaudry et al 9 reported prostaglandin E 2 (PGE 2 ) synthesis to be 10-fold higher in carcinoma tissue compared with benign prostatic hyperplasia (BPH) tissue. Whether the enzymes responsible for PGE 2 synthesis were epithelial, stromal, or vascular was not elucidated.…”

“…In continuing efforts to elucidate potentially important molecular alterations in prostate cancer development or progression, a limited number of recent investigations using both human tissues and prostate carcinoma cell lines have begun focusing on AA-metabolizing enzymes, including cyclooxygenase, 9 12-LOX, 10 5-LOX, 11 and 15-LOX-1. 12 In the current study, we have characterized the expression of 15-LOX-2 in benign prostate by immunohistochemistry, demonstrated the ability of benign prostate to form the enzymatic product of 15-LOX-2 (15-HETE) from AA, and begun exploring the possible altered expression of 15-LOX-2 and 15-HETE formation in prostate adenocarcinoma.…”

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

“…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). The data suggest a specific role for PGE2 in maintaining the growth of malignant prostatic tissues.…”