AdipoRon Affects Cell Cycle Progression and Inhibits Proliferation in Human Osteosarcoma Cells.
Journal
Journal of oncology
ISSN: 1687-8450
Titre abrégé: J Oncol
Pays: Egypt
ID NLM: 101496537
Informations de publication
Date de publication:
2020
2020
Historique:
received:
25
09
2019
accepted:
07
12
2019
entrez:
16
5
2020
pubmed:
16
5
2020
medline:
16
5
2020
Statut:
epublish
Résumé
AdipoRon (AdipoR) is the first synthetic molecule acting as a selective and potent adiponectin receptor agonist. Recently, the possible pharmacological use of AdipoR in different pathological conditions has been addressed. Interestingly, initial evidence suggests that AdipoR may have anticancer properties in different preclinical models, such as pancreatic and ovarian cancer. To our knowledge, so far no research has been directed at determining the impact of AdipoR on osteosarcoma, the most aggressive and metastatic bone malignancy occurring in childhood and adolescence age. Here, we investigate the possible antitumor effects of AdipoR in osteosarcoma cell lines. MTT and cell growth curve assays clearly indicate that AdipoR inhibits, at different extents, proliferation in both U2OS and Saos-2 osteosarcoma cell lines, the latter being more sensitive. Moreover, flow cytometry-based assays point out a significant G0/G1 phase accumulation and a contemporary S phase decrease in response to AdipoR. Consistent with the different sensitivity, a strong subG1 appearance in Saos-2 after 48 and 72 hours of treatment is also observed. The investigation of the molecular mechanisms highlights a common and initial ERK1/2 activation in response to AdipoR in both Saos-2 and U2OS cells. Interestingly, a simultaneous and dramatic downregulation of p70S6K phosphorylation, one of the main targets of mTORC1 pathway, has also been observed in AdipoR-treated Saos-2, but not in U2OS cells. Importantly, a strengthening of AdipoR-induced effects was reported upon everolimus-mediated mTORC1 perturbation in U2OS cells. In conclusion, our findings provide initial evidence of AdipoR as an anticancer molecule differently affecting various signaling pathways involved in cell cycle and cell death in osteosarcoma cells and encourage the design of future studies to further understand its pattern of activities.
Identifiants
pubmed: 32411241
doi: 10.1155/2020/7262479
pmc: PMC7204133
doi:
Types de publication
Journal Article
Langues
eng
Pagination
7262479Informations de copyright
Copyright © 2020 Luigi Sapio et al.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
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