Cytostatic effect of the hypothalamic cytokine prp-1 is mediated by mTOR and cMYc inhibition in high grade chondrosarcoma

Karina Galoian, H. Thomas Temple, Armen Galoyan

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

This study aimed to further elucidate the molecular mechanisms of antiproliferative action of proline rich polypeptide 1 (PRP-1) cytokine, produced by neurosecretory cells of the hypothalamus to be considered as alternative adjuvant therapy for metastatic chondrosarcoma, which does not respond to chemotherapy or radiation and currently without any effective treatment. Rapid cell proliferation assay of human primary cultures from high grade chondrosarcoma patients biopsies and human chondrosarcoma JJ012 cell line indicated 50 and 80% inhibition in PRP-1 treated samples correspondingly. Videomicroscopy detected that despite the treatment there are still dividing cells, meaning that cells are not in the state of dormancy, rather PRP-1 repressed the cell cycle progression, exhibited cytostatic effect. The mammalian target of rapamycin (mTOR) is an intracellular serine/threonine protein kinase that has a crucial role in a nutrient sensitive signaling pathway that regulates cell growth. Experiments with mTOR pathway after PRP-1 (10 μg/ml) treatment indicated statistically significant 30% inhibition of mTOR activity and its 56% inhibition in immunoprecipitates with PRP-1 concentrations effective for cell proliferation inhibition. Treatment with PRP- caused inhibition of mTOR and downstream target cMyc oncogenic transcription factor sufficient to trigger the cytostatic effect in high grade, but not in low grade chondrosarcomas. The fact that lower concentrations than 10 μg/ml peptide with cytostatic effect did not inhibit mTOR, but inhibited cMyc prompted us to assume that PRP-1 binds to two different receptors facilitating the antiproliferative effect.

Original languageEnglish
Pages (from-to)812-818
Number of pages7
JournalNeurochemical Research
Volume36
Issue number5
DOIs
StatePublished - May 1 2011

Fingerprint

PRP-1 peptide
Chondrosarcoma
Cytostatic Agents
Sirolimus
Cytokines
Cell proliferation
Cells
Cell Proliferation
Video Microscopy
Chemotherapy
Biopsy
Protein-Serine-Threonine Kinases
Cell growth
Therapeutics
Complementary Therapies
Cell culture
Nutrients
Hypothalamus
Assays
Cell Cycle

Keywords

  • Cell cycle
  • Chondrosarcoma
  • cMyc
  • Hypothalamus
  • mTOR
  • Primary cultures
  • Proline rich polypeptide 1

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Biochemistry

Cite this

Cytostatic effect of the hypothalamic cytokine prp-1 is mediated by mTOR and cMYc inhibition in high grade chondrosarcoma. / Galoian, Karina; Thomas Temple, H.; Galoyan, Armen.

In: Neurochemical Research, Vol. 36, No. 5, 01.05.2011, p. 812-818.

Research output: Contribution to journalArticle

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