Agents used for chemoprevention of prostate cancer may influence PSA secretion independently of cell growth in the LNCaP model of human prostate cancer progression

Peternac, Daniel; Klima, Irena; Cecchini, Marco; Schwaninger, Ruth; Studer, Urs E.; Thalmann, George N.

doi:10.1002/pros.20795

Cited by 18 publications

(19 citation statements)

References 40 publications

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“…Thus, suppression of androgen activity could be an underlying mechanism for the potential effect of certain carotenoids and tocopherols on PSA, and possibly, PrCA progression. Other mechanisms involving antioxidative and anti-inflammatory activities also have been proposed [49, 50]. …”

Section: Discussionmentioning

confidence: 99%

Plasma carotenoids and tocopherols in relation to prostate-specific antigen (PSA) levels among men with biochemical recurrence of prostate cancer

Antwi

Steck²,

Zhang

et al. 2015

Cancer Epidemiology

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Background Although men presenting with clinically localized prostate cancer (PrCA) often are treated with radical prostatectomy or radiation therapy with curative intent, about 25–40% develop biochemically recurrent PrCA within 5 years of treatment, which has no known cure. Studies suggest that carotenoid and tocopherol intake may be associated with PrCA risk and progression. We examined plasma carotenoid and tocopherol levels in relation to prostate-specific antigen (PSA) levels among men with PSA-defined biochemical recurrence of PrCA. Methods Data analyzed were from a 6-month diet, physical activity and stress-reduction intervention trial conducted in South Carolina among biochemically recurrent PrCA patients (n=39). Plasma carotenoids and tocopherol levels were measured using high-performance liquid chromatography (HPLC). Linear regression was used to estimate least-square means comparing PSA levels of men with high versus low carotenoid/tocopherol levels, adjusting for covariates. Results After adjusting for baseline PSA level, plasma cis-lutein/zeaxanthin level at 3 months was related inversely to PSA level at 3 months (P=0.0008), while α-tocopherol (P=0.01), β-cryptoxanthin (P=0.01), and all-trans-lycopene (P=0.004) levels at 3 months were related inversely to PSA levels at 6-months. Percent increase in α-tocopherol and trans-β-carotene levels from baseline to month 3 were associated with lower PSA levels at 3 and 6 months. Percent increase in β−cryptoxanthin, cislutein/zeaxanthin and all-trans-lycopene were associated with lower PSA levels at 6 months only. Conclusions Certain plasma carotenoids and tocopherols were related inversely to PSA levels at various timepoints, suggesting that greater intake of foods containing these micronutrients might be beneficial to men with PSA-defined PrCA recurrence.

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Section: Discussionmentioning

confidence: 99%

Plasma carotenoids and tocopherols in relation to prostate-specific antigen (PSA) levels among men with biochemical recurrence of prostate cancer

Antwi

Steck²,

Zhang

et al. 2015

Cancer Epidemiology

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“…This suggests that short-term treatment with isoflavones, particularly in people with highly elevated PSA levels, might not be effective. Another report observed a differential effect of genistein on PSA in different prostate cancer cells (26). Genistein inhibited PSA protein expression in both LNCaP and C4-2B cells but altered PSA mRNA expression in only LNCaP cells.…”

Section: Cell Line Studiesmentioning

confidence: 99%

Perspectives on the Role of Isoflavones in Prostate Cancer

Ahmad

Biersack

et al. 2013

AAPS J

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Abstract. Isoflavones have been investigated in detail for their role in the prevention and therapy of prostate cancer. This is primarily because of the overwhelming data connecting high dietary isoflavone intake with reduced risk of developing prostate cancer. A number of investigations have evaluated the mechanism(s) of anticancer action of isoflavones such as genistein, daidzein, biochanin A, equol, etc., in various prostate cancer models, both in vitro and in vivo. Genistein quickly jumped to the forefront of isoflavone cancer research, but the initial enthusiasm was followed by reports on its contradictory prometastatic and tumor-promoting effects. Use of soy isoflavone mixture has been advocated as an alternative, wherein daidzein can negate harmful effects of genistein. Recent research indicates a novel role of genistein and other isoflavones in the potentiation of radiation therapy, epigenetic regulation of key tumor suppressors and oncogenes, and the modulation of miRNAs, epithelial-to-mesenchymal transition, and cancer stem cells, which has renewed the interest of cancer researchers in this class of anticancer compounds. This comprehensive review article summarizes our current understanding of the role of isoflavones in prostate cancer research.

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“…In vitro, such stimuli not only induce differentiation directly but stimulate lipogenesis leading to reduced carcinogenesis by Peroxisome proliferatoractivated receptor gamma 2 (PPARγ2) (6) and increased Insulin-like growth factor (IGF) axis activity (7). Reduced levels of PSA and induction of differentiation have been observed in prostate cancer cells after treatment with flavonoids (8), genistein, seleno- L-methionine, DL-alpha-tocopherol (9), dietary components proposed for chemoprevention of prostate cancer. Restoration of DPP4 expression in prostate cancer cells reduces the malignant phenotype by blocking the bFGF pathway (10).…”

Section: Introductionmentioning

confidence: 99%

Schlafen 12 expression modulates prostate cancer cell differentiation

Kovalenko

Basson

2014

Journal of Surgical Research

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Background Schlafen proteins have previously been linked to leukocyte and intestinal epithelial differentiation. We hypothesized that Schlafen 12 (SLFN12) overexpression in prostate epithelial cells would modulate expression of prostate-specific antigen (PSA) and dipeptidyl peptidase-4 (DPP4), markers of prostatic epithelial differentiation. Materials and Methods Differentiation of the prostate cancer cell line LNCaP and PC-3 was compared after infection with an adenoviral vector coding for SLFN12-GFP (Ad-SLFN12) or GFP only expressing virus (control). Transcript levels of SLFN12, PSA and DPP4 were evaluated by RT-PCR and protein levels by Western blotting. Because Mixed Lineage Kinase (MLK) and one of its downstream effectors (ERK) have previously been implicated in some aspects of prostate epithelial differentiation, we conducted further studies in which LNCaP cells were co-treated with DMSO (control), PD98059 (ERK inhibitor) or MLK inhibitor during transfection with Ad-GFP-SLFN12 for 72 hours. Results Treatment of LNCaP or PC-3 cells with Ad-SLFN12 reduced PSA expression by 56.6±4.6% (p<0.05) but increased DPP4 transcript level by 4.8±1.0 fold (p<0.05) vs. Ad-GFP-treated controls. Further studies in LNCaP cells showed that Ad-SLFN12 overexpression increased the ratio of the mature E-cadherin protein to its precursor protein. Furthermore, SLFN12 overexpression promoted DPP4 expression either when MLK or ERK were blocked. ERK inhibition did not reverse SLFN12-induced changes in PSA, E-cadherin or DPP4. Conclusions SLFN12 may regulate differentiation in prostate epithelial cells, at least in part independently of ERK or MLK. Understanding how SLFN12 influences prostatic epithelial differentiation may ultimately identify targets to influence the phenotype of prostatic malignancy.

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Agents used for chemoprevention of prostate cancer may influence PSA secretion independently of cell growth in the LNCaP model of human prostate cancer progression

Cited by 18 publications

References 40 publications

Plasma carotenoids and tocopherols in relation to prostate-specific antigen (PSA) levels among men with biochemical recurrence of prostate cancer

Plasma carotenoids and tocopherols in relation to prostate-specific antigen (PSA) levels among men with biochemical recurrence of prostate cancer

Perspectives on the Role of Isoflavones in Prostate Cancer

Schlafen 12 expression modulates prostate cancer cell differentiation

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