Metformin prevents osteoblast-like potential and calcification in lung cancer A549 cells.
BMP-2
alkaline phosphatase activity (ALP)
calcification
lung cancer
metformin
osteoblast-like potential
Journal
Journal of biochemical and molecular toxicology
ISSN: 1099-0461
Titre abrégé: J Biochem Mol Toxicol
Pays: United States
ID NLM: 9717231
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
revised:
21
06
2023
received:
14
01
2023
accepted:
27
06
2023
medline:
10
11
2023
pubmed:
6
7
2023
entrez:
6
7
2023
Statut:
ppublish
Résumé
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.
Substances chimiques
Core Binding Factor Alpha 1 Subunit
0
Metformin
9100L32L2N
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23454Subventions
Organisme : Indian Council of Medical Research
ID : EMR-2019-665/CMB/Adhoc/BMS
Organisme : Indian Council of Medical Research
ID : EMR-2021-9936/BMS/Adhoc
Organisme : Science and Engineering Research Board
ID : CRG/2018/001559
Organisme : Science and Engineering Research Board
ID : DST/CRG/2021/002963
Organisme : Science and Engineering Research Board
ID : INT/RUS/RFBR/P-256
Organisme : Department of Biotechnology, Ministry of Science and Technology, India
ID : 6242P9/RGCB/PMD/DBT/CCML/2015
Informations de copyright
© 2023 Wiley Periodicals LLC.
Références
T. Tot, M. Gere, S. Hofmeyer, A. Bauer, U. Pellas, Semin. Cancer Biol. 2021, 72, 165.
N. Vidavsky, J. A. M. R. Kunitake, L. A. Estroff, Adv. Healthcare Mater. 2021, 10(4), 2001271.
M. Scimeca, R. Bonfiglio, F. Varone, S. Ciuffa, A. Mauriello, E. Bo nanno, Microsc. Res. Tech. 2018, 81(7), 745.
S. O'Grady, M. P. Morgan, Sci. Rep. 2019, 9(1), 542.
S. O'Grady, M. P. Morgan, Biochim. Biophys. Acta (BBA) - Rev. Cancer 2018, 1869(2), 310.
L. B. Ferreira, E. Gimba, J. Vinagre, M. Sobrinho-Simões, P. Soares, Int. J. Mol. Sci. 2020, 21(20), 7718.
D. K. Das, Diagn. Cytopathol. 2009, 37(7), 534.
M. Inomata, R. Hayashi, K. Kambara, S. Okazawa, S. Imanishi, T. Ichikawa, K. Suzuki, T. Yamada, T. Miwa, T. Kashii, S. Matsui, K. Tobe, M. Sasahara, J. Med. Case. Reports. 2012, 6(1), 279.
M. Scimeca, N. Urbano, R. Bonfiglio, O. Schillaci, E. Bonanno, Br. J. Cancer 2018, 119(9), 1129.
M. Scimeca, R. Bonfiglio, E. Menichini, L. Albonici, N. Urbano, M. T. De Caro, A. Mauriello, O. Schillaci, A. Gambacurta, E. Bonanno, Int. J. Mol. Sci. 2019, 20(22), 5633.
T. Sharma, A. Sharma, R. Maheshwari, G. Pachori, P. Kumari, C. C. Mandal, Nutr. Cancer 2020, 72(5), 873.
N. Ghosh-Choudhury, C. C. Mandal, F. Das, S. Ganapathy, S. Ahuja, G. Ghosh Choudhury, J. Biol. Chem. 2013, 288(34), 24503.
C. C. Mandal, F. Das, S. Ganapathy, S. E. Harris, G. Ghosh Choudhury, N. Ghosh-Choudhury, J. Biol. Chem. 2016, 291(3), 1148.
K. A. Hruska, S. Mathew, G. Saab, Circ. Res. 2005, 97(2), 105.
T. Sharma, A. Kapoor, C. C. Mandal, J. Cell. Physiol. 2022, 237(8), 3127.
P. Huang, A. Chen, W. He, Z. Li, G. Zhang, Z. Liu, G. Liu, X. Liu, S. He, G. Xiao, F. Huang, J. Stenvang, N. Brünner, A. Hong, J. Wang, Cell Death Discov. 2017, 3, 17039.
P. Gaur, S. Bhattacharya, S. Kant, R. S. Kushwaha, R. Garg, S. Pandey, A. Dubey, J. Cancer Res. Ther. 2020, 16(4), 839.
L. Zhang, Z. Gong, Med. Sci. Monit. 2017, 23, 4087.
A. Sharma, S. Bandyopadhayaya, K. Chowdhury, T. Sharma, R. Maheshwari, A. Das, G. Chakrabarti, V. Kumar, C. C. Mandal, PLoS One 2019, 14(1), e0209435.
Y. Lu, Y. Wang, T. Weng, Z. Chen, X. Sun, J. Wei, Z. Cai, M. Xiang, J. Diabetes Res. 2019, 2019, 1.
J. J. Sung, J. M. Ho, A. S. Lam, S. T. Yau, K. K. Tsoi, Cancer Epidemiology 2020, 69, 101808.
K. Phadwal, E. Koo, R. A. Jones, R. O. Forsythe, K. Tang, Q. Tang, B. M. Corcoran, A. Caporali, V. E. MacRae, J. Cell. Physiol. 2022, 237(11), 4303.
X. Qin, T. Jiang, S. Liu, J. Tan, H. Wu, L. Zheng, J. Zhao, J. Cell. Biochem. 2018, 119(1), 1074.
P. Saraei, I. Asadi, M. A. Kakar, Cancer Manag. Res. 2019, 11, 3295.
M.-S. Hung, M.-C. Chuang, Y.-C. Chen, C.-P. Lee, T.-M. Yang, P.-C. Chen, Y.-H. Tsai, Y.-H. Yang, Integr Cancer Ther. 2018, 52(suppl 62), PA2856.
K. Chowdhury, A. Sharma, T. Sharma, S. Kumar, C. C. Mandal, Cancer Invest. 2017, 35(6), 403.
S. Kuldeep, S. Soni, A. Srivastava, A. Mishra, L. K. Sharma, C. C. Mandal, J Gene Med. 2023, e3475.
S. Bandyopadhayaya, M. G. Akimov, R. Verma, A. Sharma, D. Sharma, G. C. Kundu, N. M. Gretskaya, V. V. Bezuglov, C. C. Mandal, J. Biochem. Mol. Toxicol. 2021, 35(4), e22693.
C. C. Mandal, T. Ghosh-Choudhury, T. Yoneda, G. G. Choudhury, N. Ghosh-Choudhury, Biochem. Biophys. Res. Commun. 2010, 402(4), 602.
J. C. Wang, J. R. Chapman, K. Wiechert, Glob. Spine J. 2016, 6(1), 1.
C. C. Mandal, N. Ghosh-Choudhury, T. Yoneda, G. G. Choudhury, N. Ghosh-Choudhury, J. Biol. Chem. 2011, 286(13), 11314.
T. Sharma, J. A. Radosevich, G. Pachori, C. C. Mandal, J. Mammary Gland Biol. Neoplasia 2016, 21(1-2), 25.
Z. Lou, W. Lin, H. Zhao, X. Jiao, C. Wang, H. Zhao, L. Liu, Y. Liu, Q. Xie, X. Huang, H. Huang, L. Zhao, Cancer Cell. Int. 2021, 21(1), 217.
R. L. Theriault, R. L. Theriault, Cancer Control 2012, 19(2), 92.
M. Scimeca, BMC Cancer 2014, 14(1), 1.
R. F. Cox, A. Hernandez-Santana, S. Ramdass, G. McMahon, J. H. Harmey, M. P. Morgan, Br. J. Cancer 2012, 106(3), 525.
F. Dane, H. M. Turk, A. Sevinc, S. Buyukberber, C. Camci, M. Tarakcioglu, J. Nat. Med. Assoc. 2008, 100(4), 425.
C. C. Mandal, S. Ganapathy, Y. Gorin, K. Mahadev, K. Block, H. E. Abboud, S. E. Harris, G. Ghosh-Choudhury, N. Ghosh-Choudhury, Biochem. J. 2011, 433(2), 393.
H. Davis, E. Raja, K. Miyazono, Y. Tsubakihara, A. Moustakas, Cytokine Growth Factor Rev. 2016, 27, 81.
N. I. Usoro, M. C. Omabbe, C. A. Usoro, A. Nsonwu, Afr. Health Sci. 2010, 10(1), 9.
Y. Iwadate, A. Suganami, Y. Tamura, T. Matsutani, S. Hirono, N. Shinozaki, T. Hiwasa, M. Takiguchi, N. Saeki, Neurosurgery 2017, 80(2), 248.
A. Mary, A. Hartemann, S. Liabeuf, C. E. Aubert, S. Kemel, J. E. Salem, P. Cluzel, A. Lenglet, Z. A. Massy, J.-D. Lalau, R. Mentaverri, O. Bourron, S. Kamel, Cardiovascular diabetology 2017, 16(1), 1.