Effects of docosahexaenoic acid and eicosapentaenoic acid on androgen-mediated cell growth and gene expression in LNCaP prostate cancer cells

Chung, Byung Ha; Mitchell, Susan H.; Zhang, Jin San; Young, Charles Y.F.

doi:10.1093/carcin/22.8.1201

Cited by 62 publications

(37 citation statements)

References 34 publications

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“…This inhibition occurred at concentrations not much greater than the ranges of the levels of PA and DHA in human serum, which are up to 30 and 12.7 mM, respectively (55,56). These results confirmed previous reports that DHA inhibits human prostate cancer cell pro- liferation (30,31,46,47). More importantly, our results indicate that PA could be a useful nutrient for dietary preventive and therapeutic approaches to human prostate cancer.…”

Section: Effects Of Rxr Ligands On the Proliferation Of Human Prostatsupporting

confidence: 91%

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Cell proliferation inhibition and alterations in retinol esterification induced by phytanic acid and docosahexaenoic acid

Tang

Suh

et al. 2007

Journal of Lipid Research

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We investigated the effects of two natural dietary retinoid X receptor (RXR) ligands, phytanic acid (PA) and docosahexaenoic acid (DHA), on proliferation and on the metabolism of retinol (vitamin A) in both cultured normal human prostate epithelial cells (PrECs) and PC-3 prostate carcinoma cells. PA and DHA inhibited the proliferation of the parental PC-3 cells and PC-3 cells engineered to overexpress human lecithin:retinol acyltransferase (LRAT) in both the absence and presence of retinol. A synthetic RXR-specific ligand also inhibited PC-3 cell proliferation, whereas all-trans retinoic acid (ATRA) did not. PA and DHA treatment increased the levels of retinyl esters (REs) in both PrECs and PC-3 cells and generated novel REs that eluted on reverse-phase HPLC at 54.0 and 50.5 min, respectively. Mass spectrometric analyses demonstrated that these novel REs were retinyl phytanate (54.0 min) and retinyl docosahexaenoate (50.5 min). Neither PA nor DHA increased LRAT mRNA levels in these cells. In addition, we demonstrate that retinyl phytanate was generated by LRAT in the presence of PA and retinol; however, retinyl docosahexaenoate was produced by another enzyme in the presence of DHA and retinol. Vitamin A (retinol) and its natural metabolites and synthetic derivatives, known as retinoids, play important roles in regulating cell proliferation, differentiation, and embryonic development (1-3). The physiological activities of retinoids are primarily carried out via nuclear receptors that transcriptionally activate certain retinoid-responsive genes. Two types of retinoid receptors have been identified, retinoic acid receptors (RARs) and retinoid X receptors (RXRs), each with three subtypes, a, b, and g (4-6). RAR/RXR heterodimers bind to specific DNA sequences known as retinoic acid response elements (7). Ligand binding of RARs and RXRs regulates the transcription of retinoic acid-responsive genes. The actions of RARs and RXRs on gene transcription also require a highly coordinated interaction with a large number of coactivators and corepressors (8).The appropriate intracellular retinoid concentrations are maintained by the activities of several metabolic enzymes (9-11). All-trans retinol (ROH; vitamin A) is the precursor of other natural retinoids. Retinol dehydrogenases oxidize ROH to all-trans retinaldehyde, and then all-trans retinaldehyde is further metabolized to all-trans retinoic acid (ATRA) by retinaldehyde dehydrogenases (11). Currently, four members of the retinaldehyde dehydrogenase family have been identified, retinaldehyde dehydrogenases 1, 2, 3, and 4 (12). ROH is converted to all-trans retinyl esters primarily by lecithin:retinol acyltransferase (LRAT), and retinyl esters (REs) are hydrolyzed to retinol by ester hydrolases (9,(13)(14)(15). REs are regarded as the storage forms of retinol (9). ATRA is oxidized to more polar metabolites, such as 4-oxo-retinoic acid, by a cytochrome P450 family member (CYP26) (16)(17)(18)(19).Retinoids are required for the appropriate differentiation of normal ro...

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Section: Effects Of Rxr Ligands On the Proliferation Of Human Prostatsupporting

confidence: 91%

“…DHA can inhibit the growth of androgenresponsive LNCaP cells (46) and androgen-unresponsive PC-3 cells and DU-145 cells (47). Lampen, Meyer, and Nau (48) reported that PA and DHA enhanced the induction of CYP26A1 expression and retinoic acid oxidation by RAR ligands in cells.…”

mentioning

confidence: 99%

Cell proliferation inhibition and alterations in retinol esterification induced by phytanic acid and docosahexaenoic acid

Tang

Suh

et al. 2007

Journal of Lipid Research

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“…Thus, serum PSA level determination is used to aid diagnosis for prostate cancer and its levels are used for monitoring response to endocrine therapies. In the presence of androgen, expression of PSA is stimulated in prostate cells, including LNCaP cells (Horoszewicz et al, 1980;Chung et al, 2001). Measurement of PSA levels in medium from LNCaP cells transfected and purified by cell sorting showed that addition of R1881 resulted in a 25-fold increase in levels of secreted PSA in cells transfected with control Adeno (Figure 5a, lanes 3, 4).…”

Section: Stable Expression Of Plzf-ar Inhibits the Expression Of Andrmentioning

confidence: 99%

Silencing of androgen-regulated genes using a fusion of AR with the PLZF transcriptional repressor

et al. 2004

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The androgen receptor (AR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors and plays a key role in the development and progression of prostate cancer. Current therapies include the use of antiandrogens aimed at inhibiting the transcriptional activation of AR-regulated genes by AR. Here, we explore a strategy aimed at obtaining silencing of ARregulated genes, based on the properties of the transcriptional repressor promyelocytic leukamia zinc-finger protein (PLZF). In order to do this, we have made a fusion protein between PLZF and AR, named PLZF-AR, and show that PLZF-AR is able to bring about silencing of genomically encoded AR-regulated genes and inhibit the androgen-regulated growth of LNCaP prostate cancer cells. Together, our results show that this strategy is able to bring about potent repression of AR-regulated responses and, therefore, could be of value in the development of new therapies for prostate cancer.

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“…In vitro and in vivo animal data suggests that the balance of n-6 and marine-derived n-3 fatty acids affects the growth of prostate cancer. Linoleic acid (n-6) has been shown to exert a stimulatory effect on the growth of androgen-responsive (LNCaP) and androgenindependent (PC-3) human prostate cancer cell lines, whereas DHA and EPA (n-3) inhibit in vitro growth (1,2,5,6). In two prior animal feeding studies, n-3-based diets reduced the growth of s.c. DU-145 xenografts in nude mice when compared with n-6-based diets (3,4).…”

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confidence: 99%

Effect of Altering Dietary ω-6/ω-3 Fatty Acid Ratios on Prostate Cancer Membrane Composition, Cyclooxygenase-2, and Prostaglandin E2

Kobayashi¹,

Barnard²,

Henning

et al. 2006

Clinical Cancer Research

154

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Purpose: To determine whether altering the dietary content of ω-6 (n-6) and ω-3 (n-3) polyunsaturated fatty acids affects the growth of androgen-sensitive prostate cancer xenografts, tumor membrane fatty acid composition, and tumor cyclooxygenase-2 and prostaglandin E2 (PGE2) levels. Experimental Design: Individually caged male severe combined immunodeficiency mice were fed isocaloric 20% kcal fat diets with the fat derived either primarily from n-6 fatty acids (n-6 group) or with the fat consisting of n-6 and n-3 fatty acids in a ratio of 1:1 (n-3 group), and injected s.c. with Los Angeles Prostate Cancer 4 (LAPC-4) cells. Tumor volumes and mouse weights were measured weekly, caloric intake was measured 3 days per week, and tumors and serum were harvested at 8 weeks postinjection. Results: Tumor growth rates, final tumor volumes, and serum prostate-specific antigen levels were reduced in the n-3 group relative to the n-6 group. The n-3 group tumors had decreased proliferation (Ki67 staining) and increased apoptosis (terminal nucleotidyl transferase–mediated nick end labeling staining). In vitro proliferation of LAPC-4 cells in medium containing n-3 group serum was reduced by 22% relative to LAPC-4 cells cultured in medium containing serum from the n-6 group. The n-6/n-3 fatty acid ratios in serum and tumor membranes were lower in the n-3 group relative to the n-6 group. In addition, n-3 group tumors had decreased cyclooxygenase-2 protein and mRNA levels, an 83% reduction in PGE2 levels, and decreased vascular endothelial growth factor expression. Conclusion: These results provide a sound basis for clinical trials evaluating the effect of dietary n-3 fatty acids from fish oil on tumor PGE2 and membrane fatty acid composition, and serum and tumor biomarkers of progression in men with prostate cancer.

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Effects of docosahexaenoic acid and eicosapentaenoic acid on androgen-mediated cell growth and gene expression in LNCaP prostate cancer cells

Cited by 62 publications

References 34 publications

Cell proliferation inhibition and alterations in retinol esterification induced by phytanic acid and docosahexaenoic acid

Cell proliferation inhibition and alterations in retinol esterification induced by phytanic acid and docosahexaenoic acid

Silencing of androgen-regulated genes using a fusion of AR with the PLZF transcriptional repressor

Effect of Altering Dietary ω-6/ω-3 Fatty Acid Ratios on Prostate Cancer Membrane Composition, Cyclooxygenase-2, and Prostaglandin E2

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