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Bone Morphogenetic Protein-Focused Strategies to Induce Cytotoxicity in Lung Cancer Cells

Bone Morphogenetic Protein-Focused Strategies to Induce Cytotoxicity in Lung Cancer Cells

Anastasios Fotinos, Narayani Nagarajan, Adriano S Martins, David T Fritz, Diane Garsetti, Annette T Lee, Charles C Hong, Melissa B Rogers

Anticancer Res. 2014 May;34(5):2095-104.

PMID: 24778011

Abstract:

Background:
High bone morphogenetic protein (BMP)-2 expression in lung carcinoma correlates with poor patient prognosis. The present study explored strategies to repress BMP signaling.
Materials and methods:
The cytotoxicity of BMP2-knockdown, dorsomorphin derivatives, and microRNAs was tested in transformed and non-transformed lung cells. Microarray analyses of 1,145 microRNAs in A549 lung adenocarcinoma cells and two other transformed lung cell types relative to BEAS-2B bronchial epithelial cells were performed.
Results:
Reduced BMP2 synthesis inhibited A549 cell growth. The dorsomorphin derivative LDN-193189, but not DMH1 or DMH4, was strongly cytotoxic towards A549 cells, but not towards BEAS-2B cells. Microarray analysis revealed that 106 miRNAs were down-regulated and 69 miRNAs were up-regulated in the three transformed lines. Three down-regulated miRNAs, hsa-mir-34b, hsa-mir-34c-3p, and hsa-miR-486-3p, repressed a BMP2 reporter gene and were cytotoxic in A549 cells, but not towards BEAS-2B cells.
Conclusion:
The observed cytotoxicity suggests that reducing BMP signaling is a useful line of attack for therapy of lung cancer.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP515880758	DMH4		515880-75-8	Price

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