IGFBP-3 Is a Metastasis Suppression Gene for Prostate Cancer.

Mehta, H H; Cobb, L J; Said, J; Lee, A; Dong, D; Kw, Lee; Cohen, P

doi:10.1210/endo-meetings.2010.part2.p4.p2-168

Cited by 4 publications

(4 citation statements)

References 21 publications

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“…The functions of IGFBP-3 have largely been explored in the context of cancer as a pivot that can determine cell fate, that is, the likelihood of survival and proliferation vs. death (2,34). In the current study, we demonstrate that IGFBP-3 may have a general anti-inflammatory effect under conditions of lipotoxic stress and that deficiency of IGFBP-3 increases IL-8, a well-known proinflammatory cytokine, and would thus be expected to contribute to the hepatic and systemic inflammatory state in patients with NAFL or NASH.…”

Section: Discussionmentioning

confidence: 99%

Suppression of IGF binding protein‐3 by palmitate promotes hepatic inflammatory responses

et al. 2016

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IGF-binding protein-3 (IGFBP-3) is a liver-derived, anti-inflammatory molecule that is decreased in obesity, a key risk factor for nonalcoholic fatty liver disease (NAFLD). It was not known whether IGFBP-3 levels were altered in NAFLD, whether such alterations could be the result of lipotoxicity, and whether altered IGFBP-3 could affect pathways that are involved in hepatic and systemic inflammation. Serum IGFBP-3 was decreased in patients with NAFLD, whereas liver and circulating IL-8 levels were increased. Palmitate inhibited IGFBP-3 secretion by THP-1 macrophages and enhanced IL-8 expression. Exposure of palmitate-treated THP-1 macrophages to IGFBP-3-deficient conditioned medium led to a 20-fold increase in palmitate-induced IL-8 expression by hepatocytes. Conversely, overexpression of IGFBP-3 suppressed JNK and NF-κB activation and blocked palmitate-induced IL-8 expression in hepatocytes. Silencing IGFBP-3 in Huh7 cells enhanced JNK and NF-κB activity and increased palmitate-induced IL-8 secretion. These data indicate that IGFBP-3 serves as an anti-inflammatory brake in hepatocytes against JNK and NF-κB and limits their activation and downstream production of proinflammatory cytokines. Under lipotoxic conditions, palmitate inhibits hepatic macrophage secretion of IGFBP-3, thereby releasing the brake and enhancing palmitate-induced IL-8 synthesis and secretion.-Min, H.-K., Maruyama, H., Jang, B. K., Shimada, M., Mirshahi, F., Ren, S., Oh, Y., Puri, P., Sanyal, A. J. Suppression of IGF binding protein-3 by palmitate promotes hepatic inflammatory responses.

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Section: Discussionmentioning

confidence: 99%

Suppression of IGF binding protein‐3 by palmitate promotes hepatic inflammatory responses

et al. 2016

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“…EMT is a genetic program whereby epithelial cells lose their polarity and adopt mesenchymal properties by disrupting cell-cell contact. In clinical settings, the transition from adenocarcinoma to CaP metastasis is correlated with EMT status [58]. On the other hand, inhibiting the expression of EMT molecules has resulted in the inhibition of metastatic potential of CaP cells [18].…”

Section: Discussionmentioning

confidence: 99%

Induction of reactive oxygen species generation inhibits epithelial–mesenchymal transition and promotes growth arrest in prostate cancer cells

Das

Suman

Damodaran

2013

Molecular Carcinogenesis

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Oxidative stress is one causative factor of the pathogenesis and aggressiveness of most of the cancer types, including prostate cancer (CaP). A moderate increase in reactive oxygen species (ROS) induces cell proliferation whereas excessive amounts of ROS promote apoptosis. In this study, we explored the pro-oxidant property of 3, 9-dihydroxy-2-prenylcoumestan [psoralidin (pso)], a dietary agent, on CaP (PC-3 and C4-2B) cells. Pso greatly induced ROS expression (more than 20-fold) that resulted in the growth inhibition of CaP cells. Overexpression of anti-oxidant enzymes superoxide dismutase 1 (SOD1), SOD2, and catalase, or pretreatment with the pharmacological inhibitor N-acetylcysteine (NAC) significantly attenuated both pso-mediated ROS generation and pso-mediated growth inhibition in CaP cells. Furthermore, pso administration significantly inhibited the migratory and invasive property of CaP cells by decreasing the transcription of β-catenin, snail, and slug, which promote epithelial mesenchymal transition (EMT), and by concurrently inducing E-cadherin expression in CaP cells. Pso-induced ROS generation in CaP cells resulted in loss of mitochondrial membrane potential, cytochrome-c release, and activation of caspase-3 and -9 and poly (ADP-ribose) polymerase (PARP), which led to apoptosis. On the other hand, overexpression of anti-oxidants rescued pso-mediated effects on CaP cells. These findings suggest that increasing the threshold of intracellular ROS could prevent or treat CaP growth and metastasis.

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“…1C). IGF binding protein 3 knockout mice (BP3KO) is another interesting model that has normal GH levels but enhanced IGF-I activity due to increased levels of free IGF-I, increased body size, and a reduced lifespan (Yakar et al, 2009;Mehta et al, 2011). BP3KO mice had a 70% decrease in plasma HN levels (Fig.…”

Section: Introductionmentioning

confidence: 99%

IGF-I regulates the age-dependent signaling peptide humanin

et al. 2014

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Summary Aging is influenced by endocrine pathways including the growth hormone/insulin-like growth factor-1 (GH/IGF) axis. Mitochondrial function has also been linked to the aging process, but the relevant mitochondrial signals mediating the effects of mitochondria are poorly understood. Humanin is a novel signaling peptide that acts as a potent regulator of cellular stress responses and protects from a variety of in vitro and in vivo toxic and metabolic insults. The circulating levels of humanin decline with age in mice and humans. Here we demonstrate a negative correlation between the activity of the GH-IGF axis and the levels of humanin, as well as a positive correlation between humanin and lifespan in mouse models with altered GH/IGF-I axis. Long-lived, GH-deficient Ames mice displayed elevated humanin levels, while short-lived GH-transgenic mice have reduced humanin levels. Furthermore, treatment with GH or IGF-I reduced circulating humanin levels in both mice and human subjects. Our results indicate that GH and IGF are potent regulators of humanin levels and that humanin levels correlate with lifespan in mice. This suggests that humanin represents a circulating mitochondrial signal that participates in modulating the aging process, adding a coordinated mitochondrial element to the endocrine regulation of aging.

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IGFBP-3 Is a Metastasis Suppression Gene for Prostate Cancer.

Cited by 4 publications

References 21 publications

Suppression of IGF binding protein‐3 by palmitate promotes hepatic inflammatory responses

Suppression of IGF binding protein‐3 by palmitate promotes hepatic inflammatory responses

Induction of reactive oxygen species generation inhibits epithelial–mesenchymal transition and promotes growth arrest in prostate cancer cells

IGF-I regulates the age-dependent signaling peptide humanin

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