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

Abstract

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.

Restoration of desmosomal junction protein expression and inhibition of H3K9-specific histone demethylase activity by cytostatic proline-rich polypeptide-1 leads to suppression of tumorigenic potential in human chondrosarcoma cells

“…We previously described the antitumorigenic effect of cytostatic PRP-1 in the JJ012 human chondrosarcoma cell line (13)(14)(15)(16). In our attempt to further elucidate the antiproliferative effect of this peptide, we conducted experiments to determine its possible role in the regulation of intercellular junctions.…”

“…JJ012 chondrosarcoma cells were cultured in a monolayer, as previously described (13)(14)(15)(16), in a medium consisting of Dulbecco's modified Eagle's medium, supplemented with F12, 10% fetal bovine serum, 25 µg/ml ascorbic acid, 100 ng/ml insulin, 100 nM hydrocortisone and 1% penicillin/streptomycin. Upon confluency, the cells were trypsinized and seeded in 6-well cluster dishes at a concentration of 1x10 6 cells/ml and incubated for 24 h in a 5% CO 2 incubator.…”

Epigenetic control of cancer by neuropeptides

“…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).…”

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

“…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.…”