Dietary n-3 polyunsaturated fatty acids fail to reduce prostate tumorigenesis in the PB-ErbB-2 x Pten<sup>+/-</sup>preclinical mouse model

Vissapragada, Sarada; Ghosh, Anup; Ringer, Lymor; Salinas, Patricia C.; Brophy, Amanda; Peaceman, Daniel; Kallakury, Bhaskar; Banerjee, Partha P.; Fricke, Stanley T.; Helfrich, William; Lee, Yi Chien; Pestell, Richard G.; Scherer, Philipp E.; Tanowitz, Herbert B.; Avantaggiati, Maria Laura; Hilakivi‐Clarke, Leena; Lisanti, Michael P.; Rodriguez, Olga; Albanese, Chris

doi:10.4161/cc.9.9.11542

Cited by 13 publications

(11 citation statements)

References 18 publications

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“…Numerous reports have shown that unsaturated FAs, such as docosahexaenoic acid and n‐3 polyunsaturated FAs (n‐3 PUFAs) induces apoptosis by upregulation of syndecan‐1 expression, and decreases phosphorylation of the 3‐phosphoinositide‐dependent kinase 1/AKT/Bad pathway . However, other studies also report that dietary n‐3 PUFAs fail to reduce tumor progression in PB‐ErbB‐2xPTEN(±) mice . The inconsistency might be oncogenic event dependent.…”

Section: Discussionmentioning

confidence: 99%

Dietary palmitate cooperates with Src kinase to promote prostate tumor progression

et al. 2019

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Numerous genetic alterations have been identified during prostate cancer progression. The influence of environmental factors, particularly the diet, on the acceleration of tumor progression is largely unknown. Expression levels and/or activity of Src kinase are highly elevated in numerous cancers including advanced stages of prostate cancer. In this study, we demonstrate that high-fat diets (HFDs) promoted pathological transformation mediated by the synergy of Src and androgen receptor in vivo. Additionally, a diet high in saturated fat significantly enhanced proliferation of Src-mediated xenograft tumors in comparison with a diet high in unsaturated fat. The saturated fatty acid palmitate, a major constituent in a HFD, significantly upregulated the biosynthesis of palmitoyl-CoA in cancer cells in vitro and in xenograft tumors in vivo. The exogenous palmitate enhanced Src-dependent mitochondrial β-oxidation. Additionally, it elevated the amount of C16-ceramide and total saturated ceramides, increased the level of Src kinase localized in the cell membrane, and Src-mediated downstream signaling, such as the activation of mitogen-activated protein kinase and focal adhesion kinase. Our results uncover how the metabolism of dietary palmitate cooperates with elevated Src kinase in the acceleration of prostate tumor progression. K E Y W O R D S palmitate/fatty acid metabolism/Src kinase/prostate cancer 1 | INTRODUCTION Prostate cancer is the most common cancer in men and one of the leading causes of cancer-related deaths in developed countries. 1 Diet is considered a critical environmental risk factor in prostate cancer progression. 2 Numerous epidemiological studies indicate that obesity, higher body mass index, or adult weight gain significantly increases the risk of aggressive prostate cancer, mortality, and recurrence of prostate cancer. 3-8 A high-fat diet (HFD) or certain dietary saturated fatty acids (FAs) including palmitic acid (PA) and myristic acid (MA) are associated with advanced stages of prostate cancer and increase the risk of prostate cancer-specific mortality. 3,5,7,9 Incorporation of excess free FAs into cancer cell membranes promotes cancer invasion by reduction of cell-cell contact and increase of surface adhesion. 10 However, the interaction of dietary factors with oncogenic events to regulate tumor progression is not well-understood. Numerous genetic alterations including aberrant expression and/ or loss of tumor suppressor genes have been identified in the initiation and progression of prostate tumors. 11 Among those oncogenic events, overexpression and/or activation of Src kinase is common in advanced stages of prostate cancer. 12,13 Src kinase is a pleiotropic activator to mediate numerous signal transduction pathways initiated by G-protein coupled receptors, β1-integrin, growth factor receptors, and others. 14,15 The activation of Src kinase promotes cell survival, proliferation, migration, and invasion in The Prostate. 2019;79:896-908. wileyonlinelibrary.com/journal/pros

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Section: Discussionmentioning

confidence: 99%

Dietary palmitate cooperates with Src kinase to promote prostate tumor progression

et al. 2019

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“…The slides were blocked for 20 min and incubated overnight at 4°C with the primary antibody. Detection was performed as previously described 13 , 31 - 34 . Because of the small sample size statistical analyses were performed using the Mann-Whitney U test and actual p values are shown.…”

Section: Methodsmentioning

confidence: 99%

Quantifying the CDK inhibitor VMY-1-103’s activity and tissue levels in an in vivo tumor model by LC-MS/MS and by MRI

et al. 2012

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The development of new small molecule-based therapeutic drugs requires accurate quantification of drug bioavailability, biological activity and treatment efficacy. Rapidly measuring these endpoints is often hampered by the lack of efficient assay platforms with high sensitivity and specificity. Using an in vivo model system, we report a simple and sensitive liquid chromatography-tandem mass spectrometry assay to quantify the bioavailability of a recently developed novel cyclin-dependent kinase inhibitor VMY-1-103, a purvalanol B-based analog whose biological activity is enhanced via dansylation. We developed a rapid organic phase extraction technique and validated wide and functional VMY-1-103 distribution in various mouse tissues, consistent with its enhanced potency previously observed in a variety of human cancer cell lines. More importantly, in vivo MRI and single voxel proton MR-Spectroscopy further established that VMY-1-103 inhibited disease progression and affected key metabolites in a mouse model of hedgehog-driven medulloblastoma.

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“…158), although dietary n-3 polyunsaturated fatty acids failed to reduce prostate tumorigenesis in a preclinical mouse model. 159 A recent case-control study found a strong association between high intake of long chain n-3 PUFA and decreased risk of aggressive prostate cancer. 158 Furthermore, this study identified a SNP in the COX-2 gene that, along with low dietary intake of n-3 PUFA, had an increased risk of prostate cancer (OR = 5.49; 95% CI: 1.80-16.7).…”

Section: Pia As a Precursor Lesion To Prostate Cancermentioning

confidence: 99%

“…Just as proinflammatory n‐6 polyunsaturated fatty acids (PUFA) may confer an increased risk of prostate cancer, the anti‐inflammatory n‐3 (omega 3) PUFA has been associated with a decreased risk (reviewed in Ref. 158), although dietary n‐3 polyunsaturated fatty acids failed to reduce prostate tumorigenesis in a preclinical mouse model 159 . A recent case–control study found a strong association between high intake of long chain n‐3 PUFA and decreased risk of aggressive prostate cancer 158 .…”

Section: Anti‐inflammatory Compounds and Prostate Cancer Riskmentioning

confidence: 99%

Prostate cancer and inflammation: the evidence

Sfanos¹,

2011

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Chronic inflammation is now known to contribute to several forms of human cancer, with an estimated 20% of adult cancers attributable to chronic inflammatory conditions caused by infectious agents, chronic noninfectious inflammatory diseases and / or other environmental factors. Indeed, chronic inflammation is now regarded as an ‘enabling characteristic’ of human cancer. The aim of this review is to summarize the current literature on the evidence for a role for chronic inflammation in prostate cancer aetiology, with a specific focus on recent advances regarding the following: (i) potential stimuli for prostatic inflammation; (ii) prostate cancer immunobiology; (iii) inflammatory pathways and cytokines in prostate cancer risk and development; (iv) proliferative inflammatory atrophy (PIA) as a risk factor lesion to prostate cancer development; and (v) the role of nutritional or other antiinflammatory compounds in reducing prostate cancer risk.

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Dietary n-3 polyunsaturated fatty acids fail to reduce prostate tumorigenesis in the PB-ErbB-2 x Pten^+/-preclinical mouse model

Cited by 13 publications

References 18 publications

Dietary palmitate cooperates with Src kinase to promote prostate tumor progression

Dietary palmitate cooperates with Src kinase to promote prostate tumor progression

Quantifying the CDK inhibitor VMY-1-103’s activity and tissue levels in an in vivo tumor model by LC-MS/MS and by MRI

Prostate cancer and inflammation: the evidence

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Dietary n-3 polyunsaturated fatty acids fail to reduce prostate tumorigenesis in the PB-ErbB-2 x Pten+/-preclinical mouse model

Cited by 13 publications

References 18 publications

Dietary palmitate cooperates with Src kinase to promote prostate tumor progression

Dietary palmitate cooperates with Src kinase to promote prostate tumor progression

Quantifying the CDK inhibitor VMY-1-103’s activity and tissue levels in an in vivo tumor model by LC-MS/MS and by MRI

Prostate cancer and inflammation: the evidence

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Dietary n-3 polyunsaturated fatty acids fail to reduce prostate tumorigenesis in the PB-ErbB-2 x Pten^+/-preclinical mouse model