Affiliation:
1. Department of Biochemistry, School of Life Sciences Central University of Rajasthan Ajmer Rajasthan India
2. Centre for Innovation, Research & Development, Dr. B. Lal Clinical Laboratory Pvt Ltd. Jaipur Rajasthan India
3. Department of Molecular Medicine and Biotechnology Sanjay Gandhi Post Graduate Institute of Medical Sciences Lucknow Uttar Pradesh India
Abstract
AbstractIn spite of recent advances made in understanding its progression, cancer is still a leading cause of death across the nations. Molecular pathophysiology of these cancer cells largely differs depending on cancer types and even within the same tumor. Pathological mineralization/calcification is seen in various tissues including breast, prostate, and lung cancer. Osteoblast‐like cells derived after trans‐differentiation of mesenchymal cells usually drive calcium deposition in various tissues. This study aims to explore the presence of osteoblast‐like potential in lung cancer cells and its prevention. ALP assay, ALP staining, nodule formation, RT‐PCR, RT‐qPCR, and western blot analysis experiments were carried out in lung cancer A549 cells to achieve said objective. Expressions of various osteoblast markers (e.g., ALP, OPN, RUNX2, and Osterix) along with osteoinducer genes (BMP‐2 and BMP‐4) were observed in A549 cells. Moreover, ALP activity and ability leading to nodule formation revealed the presence of osteoblast‐like potential in lung cancer cells. Here, BMP‐2 treatment increased expressions of osteoblast transcription factors such as RUNX2 and Osterix, enhanced ALP activity, and augmented calcification in this cell line. It was also observed that antidiabetic metformin inhibited BMP‐2 mediated increase in osteoblast‐like potential and calcification in these cancer cells. The current study noted that metformin blocked BMP‐2 mediated increase in epithelial to mesenchymal transition (EMT) in A549 cells. The above findings for the first time unravel that A549 cells possess osteoblast‐like potential which drives lung cancer calcification. Metformin might prevent BMP‐2 induced osteoblast‐like phenotype of the lung cancer cells with concomitant inhibition of EMT to inhibit lung cancer tissue calcification.
Funder
Indian Council of Medical Research
Science and Engineering Research Board
Department of Biotechnology, Ministry of Science and Technology, India
Subject
Health, Toxicology and Mutagenesis,Toxicology,Molecular Biology,Molecular Medicine,Biochemistry,General Medicine
Cited by
1 articles.
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