Myc-oncogene Inactivating Effect by Proline Rich Polypeptide (PRP-1) in Chondrosarcoma JJ012 Cells

Galoian, Karina; Scully, Sean P.; Galoyan, A. A.

doi:10.1007/s11064-008-9794-6

Cited by 20 publications

(30 citation statements)

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“…Strong antibacterial (in vivo) and antiviral (in vitro) properties of hypothalamic proline rich peptides [3] as well as antineurodegenerative [4] and their immunotropic properties [5] provide evidence for the existence of brain protective mechanisms against infection, neurodegeneration, immunodeficiencies [6] and tumor. We demonstrated that PRP-1 induced decay of tumor cells L929 and decreased mitotic activity of those transformed mouse fibroblast cells [1,[7][8][9][10]. Taking into consideration our preliminary data on antitumor (especially effect on sarcoma C45, where shrinkage of tumor was observed after subcutaneous injection of PRP-1), we proceeded with investigation of the PRP-1 effect on chondrosarcoma.…”

Section: Introductionmentioning

confidence: 99%

“…Currently, metastatic chondrosarcoma has no effective treatment, leaving the option of surgical resection -therefore a new approach in adjuvant systemic therapy for this tumor is urgently needed. Our experimental results demonstrated inactivation, abolishment of Myc-luc activity (usually highly upregulated in chondrosarcoma cells,) when treated with low concentration (0.5-1 lg/ml) PRP-1 [10]. Inactivation of a single oncogene can induce cancer cells to differentiate into cells with a normal phenotype or to undergo, cellular senescence and/or apoptosis [11].…”

Section: Introductionmentioning

confidence: 99%

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Antitumorigenic Effect of Brain Proline Rich Polypeptide-1 in Human Chondrosarcoma

et al. 2009

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Proline rich polypeptide (PRP-1) produced by neurosecretory cells of the hypothalamus is one of the fragments of neurophysin-vasopressin-associated glycoprotein. The primary structure of the neuropeptide PRP-1 isolated from neurosecretory granules of bovine neurohypophysis. We investigated PRP-1 action on chondrosarcoma, the second most common malignancy in bone, which primarily affects the cartilage cells. This deadly disease does not have any effective treatment. Earlier we demonstrated MYC oncogene inactivating effect by 1 lg/ml concentration brain PRP-1 In the present study we observed reduced viable sarcoma JJ012 cell numbers in comparison with control (89% growth inhibition) when treated with low concentrations of PRP-1 (0.5–1 lg/ml). Higher concentrations did not exhibit inhibitory effect. We assume that PRP-1 in low concentration impedes cell cycle progression. The fact that low concentrations of PRP-1 abolished Myc activity prompts to think that the antitumorigenic effect of PRP-1 in low concentrations is mediated through oncogene inactivation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antitumorigenic Effect of Brain Proline Rich Polypeptide-1 in Human Chondrosarcoma

et al. 2009

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“…The antimicrobial, antitumorigenic and antineurodegenerative properties for this immunomodulatory cytokine were previously reported (22) and the quantification of hypothalamic PRP-1 in the blood was recently documented (23). Furthermore, our prevous studies described that PRP-1, mammalian target of rapamycin complex 1 inhibitor, exerts antiproliferative cytostatic effects in chondrosarcoma (7)(8)(9)24) and breast cancer cells (10).…”

Section: Neuropeptides Involved In Epigenetic Control Of Cancermentioning

confidence: 71%

“…The stemness markers, targets of the miR302C polycomb protein, BMI-1, NANOG (28) and c-Myc (8,24,28), were markedly downregulated by PRP-1 (28). Interestingly, PRP-1 demonstrated the inhibition of giant cell tumors of the bone and, conversely, supported the growth of human normal bone marrow stromal cells (31).…”

Section: Neuropeptides Involved In Epigenetic Control Of Cancermentioning

confidence: 99%

Epigenetic control of cancer by neuropeptides

Galoian

Patel

2016

Biomedical Reports

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Abstract. Neuropeptides act as neurohormones, neurotransmitters and/or neuromodulators. Neuropeptides maintain physiological homeostasis and are paramount in molecular mechanisms of disease progression and regulation, including in cancer. Neuropeptides, by their definition, originate and are secreted from the neuronal cells, they are able to signal to neighboring cells or are released into the blood flow, if they act as neurohormones. The majority of neuropeptides exert their functions through G protein-coupled receptors, with certain exceptions. Although previous studies indicate that neuropeptides function in supporting proliferation of malignant cells in many types of solid tumor, the antitumorigenic action of the neuropeptides and their receptors, for example, in gastric cancers and chondrosarcoma, were also reported. It is known that epigenetically modified chromatin regulates molecular mechanisms involved in gene expression and malignant progression. The epigenetic modifications are genetically heritable, although they do not cause changes in DNA sequence. DNA methylation, histone modifications and miRNA expression are subject to those modifications. While there is substantial data on epigenetic regulation of neuropeptides, the epigenetic control of cancer by neuropeptides is considered to be uncharted territory. The aim of the current review is to describe the involvement of neuropeptides in the epigenetic machinery of cancer based on data obtained from our laboratory and from other authors.

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“…Understanding the differences in their expression patterns between the normal and malignant states, and the signaling pathways that lead to these differences, require further investigation as important targets for future therapeutic interventions. Metastatic chondrosarcoma does not respond to conventional therapies and the search for new therapeutic approaches is urgent (2)(3)(4)(5)(6)(7)(8)(9)(10)36,46). The ability of PRP-1 as an antiproliferative agent to restore the expression of anti-inflammatory cytokines with tumor suppressor function proves the importance of this neuropeptide for future clinical consideration.…”

Section: Discussionmentioning

confidence: 99%

Effect of cytostatic proline rich polypeptide-1 on tumor suppressors of inflammation pathway signaling in chondrosarcoma

Galoian

Luo

Qureshi

et al. 2016

Molecular and Clinical Oncology

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Abstract. Cytokines produced in the tumour microenvironment exert an important role in cancer pathogenesis and in the inhibition of disease progression. Cancer of the cartilage is termed metastatic chondrosarcoma; however, the signaling events resulting in mesenchymal cell transformation to sarcoma have yet to be fully elucidated. The present study aimed to characterize the cytokine expression profile in the human JJ012 chondrosarcoma cell line, as well as the effect of cytostatic proline-rich polypeptide-1 (PRP-1). Western blot experiments demonstrated that the levels of suppressor of cytokine signaling 3 (SOCS3) were upregulated in chondrocytes compared with chondrosarcoma cells. Addition of PRP-1 restored the expression of the tumor suppressors, SOCS3 and ten-eleven-translocation methylcytosine dioxygenase 1 and 2 (TET1/2), in a dose-responsive manner. It is known that methylation of histone H3K9 was eliminated from the promoters of the inflammation-associated genes. PRP-1 inhibited H3K9 demethylase activity with an IC 50 (concentration required to give half-maximal inhibition) value of 3.72 µg/ml in the chondrosarcoma cell line. Data obtained from ELISA experiments indicated that the expression of interleukin-6 (IL-6) in chondrosarcoma cells was 86-fold lower compared with that in C28 chondrocytes. In the present study, a 53-fold downregulation of IL-6 expression in co-culture of chondrosarcoma cells and C28 chondrocytes was identified as well. Downregulation of IL-6 expression has been documented in numerous other tumor types, although the reasons for this have not been fully established. In chondrosarcoma, IL-6 manifests itself as an anti-inflammatory agent and, possibly, as an anti-tumorigenic factor. To explore protein-DNA interactions leading to such differences, a gel-shift chemiluminescent assay was performed. Gel shifts were observed for chondrosarcoma and chondrocytes in the lanes that contained nuclear cell extract and oligo-IL-6 DNA. Notably, the DNA-protein complexes in C28 chondrocytes were markedly larger compared with those in chondrosarcoma cells. The mechanisms that underpin such differences, and characterization of the interacting proteins, remain to be fully elucidated.

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Myc-oncogene Inactivating Effect by Proline Rich Polypeptide (PRP-1) in Chondrosarcoma JJ012 Cells

Cited by 20 publications

References 17 publications

Antitumorigenic Effect of Brain Proline Rich Polypeptide-1 in Human Chondrosarcoma

Antitumorigenic Effect of Brain Proline Rich Polypeptide-1 in Human Chondrosarcoma

Epigenetic control of cancer by neuropeptides

Effect of cytostatic proline rich polypeptide-1 on tumor suppressors of inflammation pathway signaling in chondrosarcoma

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