Pomegranate extract inhibits androgen-independent prostate cancer growth through a nuclear factor-κB-dependent mechanism

Rettig, Matthew B.; Heber, David; An, Jiabin; Seeram, Navindra P.; Rao, Jian Yu; Liu, Huiren; Klatte, T.; Belldegrun, Arie S.; Moro, Aune; Henning, Susanne M.; Mo, Deqiong; Aronson, William J.; Pantuck, Allan J.

doi:10.1158/1535-7163.mct-08-0136

Cited by 126 publications

(107 citation statements)

References 37 publications

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“…5). Our results are in line with evidence that points to a pathophysiologic role for NF-jB in PCa [48]. This factor was also associated with high expression of MMP9 and VEGF in PCa [49].…”

Section: Discussionsupporting

confidence: 92%

Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer

et al. 2011

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Prostate cancer (PCa) is the second leading cause of cancer-associated death in men. Once a tumor is established it may attain further characteristics via mutations or hypoxia, which stimulate new blood vessels. Angiogenesis is a hallmark in the pathogenesis of cancer and inflammatory diseases that may predispose to cancer. Heme oxygenase-1 (HO-1) counteracts oxidative and inflammatory damage and was previously reported to play a key role in prostate carcinogenesis. To gain insight into the anti-tumoral properties of HO-1, we investigated its capability to modulate PCa associated-angiogenesis. In the present study, we identified in PC3 cells a set of inflammatory and pro-angiogenic genes down-regulated in response to HO-1 overexpression, in particular VEGFA, VEGFC, HIF1α and α5β1 integrin. Our results indicated that HO-1 counteracts oxidative imbalance reducing ROS levels. An in vivo angiogenic assay showed that intradermal inoculation of PC3 cells stable transfected with HO-1 (PC3HO-1) generated tumours less vascularised than controls, with decreased microvessel density and reduced CD34 and MMP9 positive staining. Interestingly, longer term grown PC3HO-1 xenografts displayed reduced neovascularization with the subsequent down-regulation of VEGFR2 expression. Additionally, HO-1 repressed nuclear factor κB (NF-κB)-mediated transcription from an NF-κB responsive luciferase reporter construct, which strongly suggests that HO-1 may regulate angiogenesis through this pathway. Taken together, these data supports a key role of HO-1 as a modulator of the angiogenic switch in prostate carcinogenesis ascertaining it as a logical target for intervention therapy.

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“…5). Our results are in line with evidence that points to a pathophysiologic role for NF-jB in PCa [48]. This factor was also associated with high expression of MMP9 and VEGF in PCa [49].…”

Section: Discussionsupporting

confidence: 92%

Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer

et al. 2011

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“…We have also shown that PE blocks NF-kB activity in prostate cancer models both in vitro and in vivo [14]. Inhibition of JNK by PE in immune cells has been demonstrated as well [15].…”

Section: Introductionmentioning

confidence: 57%

WITHDRAWN: Pomegranate extract inhibits EMT in clear cell renal cell carcinoma in a NF-κB and JNK dependent manner

An¹,

Guo²,

Wang³

et al. 2014

Asian Journal of Urology

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Objective: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC) and is characterized by biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. One effect of VHL inactivation is hypoxia inducible factor alpha (HIFa)-independent constitutive activation of nuclear factor kappa B (NF-kB) and c-jun N-terminal kinase (JNK). Both NF-kB and JNK drive ccRCC growth and epithelial to mesenchymal transition (EMT). The purpose of this study was to determine the biochemical effects of pomegranate juice extracts (PE) on RCC cell lines. Methods: The pre-clinical effects of PE on NF-kB, JNK, and the EMT phenotype were assayed, including its effect on proliferation, anchorage-independent growth, and invasion of pVHLdeficient RCCs. Results: PE inhibits the NF-kB and JNK pathways and consequently inhibits the EMT phenotype of pVHL-deficient ccRCCs. The effects of PE are concentration-dependent and affect not only biochemical markers of EMT (i.e., cadherin expression) but also functional manifestations of EMT, such as invasion. These effects are manifested within days of exposure to PE when diluted 2000-fold. Highly dilute concentrations of PE (10 6 dilution), which do not impact these pathways in the short term, were found to have NF-kB and JNK inhibitory effects and ability to reverse the EMT phenotype following prolonged exposure. Conclusion: These findings suggest that PE may mediate inhibition growth of pVHL-deficient ccRCCs and raises the possibility of its use as a dietary adjunct to managing patients with * Corresponding authors. E-mail addresses: apantuck@mednet.ucla.edu (A.J. Pantuck), mrettig@mednet.ucla.edu (M.B. Rettig). Peer review under responsibility of Chinese Urological Association and SMMU. + MODEL Please cite this article in press as: An J, et al., Pomegranate extract inhibits EMT in clear cell renal cell carcinoma in a NF-kB and JNK dependent manner, Asian Journal of Urology (2015), http://dx.

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“…Over the past few years, consumer demand-based research on functional foods gave a basis for traditional using of pomegranate, which lead to an increase in number of scientific papers concerning pomegranate and its products with health-improving effects (Mehta & Lansky, 2004;Rettig et al, 2008;Turk et al, 2008;Alam et al, 2010;Dai et al, 2010;Jadeja et al, 2010;Park et al, 2010). The reports have focused on in vitro, ex vivo, and in vivo antioxidant actions, of pomegranate and its products, which are attributed to the chemical composition.…”

Section: Antioxidant Activitymentioning

confidence: 99%