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. 2023 Nov;37(11):e23454.
doi: 10.1002/jbt.23454. Epub 2023 Jul 6.

Metformin prevents osteoblast-like potential and calcification in lung cancer A549 cells

Pooja Yadav  1 , Sweta Makwana  1 , Shivani Bansal  1 , Sneha Soni  1 , Manas K Mahapatra  1 , Shreetama Bandyopadhayaya  1 , Rashmi Tailor  1 , Sandeep K Shrivastava  2 , Lokendra K Sharma  3 , Chandi C Mandal  1
Affiliations

Metformin prevents osteoblast-like potential and calcification in lung cancer A549 cells

Pooja Yadav et al. J Biochem Mol Toxicol. 2023 Nov.

Abstract

In 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.

Keywords: BMP-2; alkaline phosphatase activity (ALP); calcification; lung cancer; metformin; osteoblast-like potential.

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