The Effects of Astaxanthin on Proliferation and Differentiation of MG-63 Osteosarcoma Cells via Aryl Hydrocarbon Receptor (AhR) Pathway: A Comparison with AhR Endogenous Ligand

Abstract

Background: Osteosarcoma (OS) is the most prevalent bone-related malignancy with a high mortality rate among children and adolescents. In the present study, first we explored the effects of astaxanthin (AST) on proliferation and differentiation of the MG-63 osteosarcoma cell line, and then compared its effects with AhR endogenous ligand (FICZ).

Methods: Cell proliferation and cytotoxicity assay were performed using MTT. To identify possible mechanisms underlying AST-induced changes in osteogenic metabolism via the AHR pathway, we defined changes in CYP1A1, osteocalcin, osteopontin, type I collagen, and Runx2 gene expression using RT-PCR.

Results: AST upregulated CYP1A1, osteocalcin, osteopontin, type I collagen, and Runx2 expression in trends of increasing its concentration. FICZ showed a biphasic effect on MG-63 cell proliferation. At high concentrations, it significantly decreased the cell viability, while at lower concentrations it was increased as compared to the control. Increasing FICZ concentrations from 1 nm to 1 μM, down-regulated the expression of Runx2, osteopontin, osteocalcin and collagen type 1 at the transcriptional levels. It seems that AST can augment the proliferation and differentiation of MG-63 via the AhR-dependent pathway, while FICZ suppresses the proliferation and differentiation of MG-63.

Conclusion: We concluded that various AhR ligands show different behaviors in the modulation of MG-63 cells.

Additional information

Funding

This work was supported by the Shiraz University of Medical Sciences [No. 1396-01-33-14152].

Notes on contributors

Nima Montazeri-Najafabady

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. The present manuscript was adapted from project No. 1396-01-33-14152 approved by the Shiraz University of Medical Sciences. The authors would like to thank Dr. Nasrin Shokrpour for editorial assistance.

Mohammad Hossein Dabbaghmanesh

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. The present manuscript was adapted from project No. 1396-01-33-14152 approved by the Shiraz University of Medical Sciences. The authors would like to thank Dr. Nasrin Shokrpour for editorial assistance.

Mohammad Reza Arabnezhad

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. The present manuscript was adapted from project No. 1396-01-33-14152 approved by the Shiraz University of Medical Sciences. The authors would like to thank Dr. Nasrin Shokrpour for editorial assistance.