Megestrol acetate induced proliferation and differentiation of osteoblastic MC3T3-E1 cells: A drug repurposing approach.

Autor: Badran SA; Department of Pediatric Dentistry and Orthodontics, Faculty of Dentistry, University of Jordan, Amman 11942, Jordan., Atia-Tul-Wahab; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: tulwahab@yahoo.com., Fayyaz S; H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan., Taj B; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan., Choudhary MI; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Electronic address: iqbal.choudhary@iccs.edu.
Jazyk: angličtina
Zdroj: Steroids [Steroids] 2020 May; Vol. 157, pp. 108607. Date of Electronic Publication: 2020 Feb 19.
DOI: 10.1016/j.steroids.2020.108607
Abstrakt: Aims: Drug repurposing or repositioning i.e.; identifying new indications for existing drugs have recently accelerated the process of drug discovery and development. Megestrol acetate (1) is a well-known progestin. It is commonly used as an appetite stimulant, and also in the treatment of breast, and endometrial cancers. The aim of this study is to investigate the effect of megestrol acetate (1) in osteoblast differentiation, and to determine the possible mechanism involved in megestrol acetate (1) induced osteoblast differentiation.
Main Methods: Cytotoxicity of different steroidal drugs was evaluated using MTT assay. Alkaline phosphatase (ALP) activity was also determined, and alizarin red S (ARS) staining was performed to measure extracellular mineralization. Osteogenic protein levels were determined using Western blot analysis.
Key Findings: Results of the current study indicated that the megestrol acetate (1) enhanced the proliferation and differentiation of osteoblast cells at 1, 0.2, and 0.04 µM. This stimulatory effect of the megestrol acetate (1) was more prominent at 0.2 µM for cell proliferation, while the maximum cell differentiation (ALPase activity, and calcification) was observed at 0.04 μM. Western blot analysis also showed that megestrol acetate (1) altered the expression of bone morphogenic protein-2 (BMP2), p38, and pJNK proteins. Hence, only moderate doses of MGA (1) can enhance osteoblast proliferation and differentiation.
Significance: Our results identified that megestrol acetate (1) could be a potential lead for further research towards bone fragility related disorders.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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