Dietary gamma-linolenate attenuates tumor growth in a rodent model of prostatic adenocarcinoma via suppression of elevated generation of PGE(2) and 5S-HETE.

Prostate cancer poses considerable threat to the aging male population as it has become a leading cause of cancer death to this group. Due to the complexity of this age-related disease, the mechanism(s) and factors resulting in prostate cancer remain unclear. Reports showing an increase risk in prostatic cancer with increasing dietary fat are contrasted by other studies suggesting the beneficial effects of certain polyunsaturated fatty acid (PUFA) in the modulation of tumor development.

15-lipoxygenase metabolites of gamma-linolenic acid/eicosapentaenoic acid suppress growth and arachidonic acid metabolism in human prostatic adenocarcinoma cells: possible implications of dietary fatty acids.

Although gammalinolenic acid (GLA) and eicosapentaenoic acid (EPA) have independently been reported to suppress growth of cancer cells, their relative potencies are unknown. To determine the possible attenuating efficacies of dietary GLA or EPA on prostate carcinogenesis, we hereby report the in vitro effects of GLA, EPA and their 15-lipoxygenase (15-LOX) metabolites: 15(S)-HETrE and 15(S)-HEPE, respectively, on growth and arachidonic acid (AA) metabolism in human androgen-dependent (LNCaP) and androgen-independent (PC-3) prostatic cancer cells in culture. Specifically, both cells were preincubated respectively with the above PUFAs.

Suppression of cyclooxygenase-2 overexpression by 15S-hydroxyeicosatrienoic acid in androgen-dependent prostatic adenocarcinoma cells.

Emerging reports now implicate alterations of arachidonic acid (AA) metabolism with prostate carcinogenesis. To test this hypothesis, androgen-primed benign hyperplastic (BHC) and malignant tumorigenic (MTC) cells derived from the Lobund-Wistar rat model of autochthonous prostate adenocarcinoma were incubated with (14)C-AA. Our data using MTCs revealed enhanced dual metabolism of (14)C-AA via COX to generate increased PGE(2) and via 5-lipoxygenase (LOX) to generate increased 5S-HETE in tumorigenic cells.

Suppression of leukotriene B4 generation by ex-vivo neutrophils isolated from asthma patients on dietary supplementation with gammalinolenic acid-containing borage oil: possible implication in asthma.

Dietary gammalinolenic acid (GLA), a potent inhibitor of 5-lipoxygenase (5-LOX) and suppressor of leukotriene B4 (LTB4), can attenuate the clinical course of rheumatoid arthritics, with negligible side effects. Since Zileuton, also an inhibitor of 5-LOX, attenuates asthma but with an undesirable side effect, we investigated whether dietary GLA would suppress biosynthesis of PMN-LTB4 isolated from asthma patients and attenuate asthma. Twenty-four mild-moderate asthma patients (16-75 years) were randomized to receive either 2.

5 alpha-reductase-catalyzed conversion of testosterone to dihydrotestosterone is increased in prostatic adenocarcinoma cells: suppression by 15-lipoxygenase metabolites of gamma-linolenic and eicosapentaenoic acids.

Although the androgens, testosterone (T) and its highly active metabolite dihydrotestosterone (DHT) play a role in the development and progression of prostate cancer, the mechanism(s) are unclear. Furthermore, 5 alpha-reductase which catalyze the conversion of T to DHT, has been a target of manipulation in the treatment of prostatic cancer, hence synthetic 5 alpha-reductase activity inhibitors have shown therapeutic promise. To demonstrate that nutrients derived from dietary sources can exert similar therapeutic promise, this study was designed using benign hyperplastic cells (BHC) and malignant tumorigenic cells (MTC) derived from Lobund-Wistar (L-W) rat model of prostatic adenocarcinoma to test the effects of gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and their 15-lipoxygenase metabolites on cellular 5 alpha-reductase activity.

Biological significance of essential fatty acids/prostanoids/lipoxygenase-derived monohydroxy fatty acids in the skin.

The skin displays a highly active metabolism of polyunsaturated fatty acids (PUFA). Dietary deficiency of linoleic acid (LA), an 18-carbon (n-6) PUFA, results in characteristic scaly skin disorder and excessive epidermal water loss. Although arachidonic acid (AA), a 20-carbon (n-6) PUFA, is metabolized via cyclooxygenase pathway into predominantly prostaglandin E2 (PGE2) and PGF2alpha, the metabolism of AA via the 15-lipoxygenase (15-LOX) pathway, which is very active in skin epidermis and catalyzes the transformation of AA into predominantly 15S-hydroxyeicosatetraenoic acid (15S-HETE).

Cyclic-AMP agonists inhibit antiphospholipid/beta2-glycoprotein I induced synthesis of human platelet thromboxane A2 in vitro.

Objective: To investigate mechanisms responsible for increased thrombotic activity in systemic lupus erythematosus (SLE) associated with the antiphospholipid syndrome (APS). We had reported that anticardiolipin/beta2-glycoprotein I (aCL/beta2-GPI) complexes induce platelet overactivity resulting in excessive production of thromboxane A2 (TXA2). Presumably this occurs by decreased platelet cyclic AMP (cAMP) activity and results in increased platelet aggregation.

Activation of peroxisome proliferator-activated receptor (PPAR)-gamma by 15S-hydroxyeicosatrienoic acid parallels growth suppression of androgen-dependent prostatic adenocarcinoma cells.

Although dietary gamma-linolenic acid (GLA) and its 15-lipoxygenase metabolite, 15S-hydroxyeicosatrienoic acid (15S-HETrE), have been reported to exert antiproliferative activities in other systems, their role in prostatic carcinogenesis is unknown. To evolve a possible mechanism for the suppressive effect on growth of prostatic cells, we incubated GLA and 15S-HETrE with androgen-dependent prostatic adenocarcinoma cells. 15S-HETrE but not GLA markedly inhibited [(3)H]thymidine uptake in parallel with the upregulation of peroxisome proliferator-activated receptor-gamma expression (a growth modulating nuclear receptor).

Inhibition of TNFalpha-induced cyclooxygenase-2 expression by amentoflavone through suppression of NF-kappaB activation in A549 cells.

Amentoflavone, a biflavonoid with antiinflammatory activity, downregulates COX-2 expression in TNFalpha-activatedA549 cells with concomitant inhibition of NF-kappaB mediated signaling cascades. We demonstrate here that amentoflavone inhibits NF-kappaB/ DNA binding activity potently along with inhibition of degradation of IkappaBalpha and NF-kappaB translocation into nucleus in TNFalpha-activated A549 cells. This flavonoid upregulates PPAR gamma, a transcription factor involved in repressing many cytokine-induced gene expressions.