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

Research output: Contribution to journalArticle

19 Scopus citations

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 upregulated 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.

Original languageEnglish (US)
Pages (from-to)2095-2104
Number of pages10
JournalAnticancer Research
Volume34
Issue number5
StatePublished - May 1 2014

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • Bone morphogenetic proteins
  • Cell proliferation
  • Cell survival
  • Lung neoplasms
  • MicroRNAs
  • Preclinical drug evaluation
  • RNA interference

Fingerprint Dive into the research topics of 'Bone morphogenetic protein-focused strategies to induce cytotoxicity in lung cancer cells'. Together they form a unique fingerprint.

  • Cite this

    Fotinos, A., Nagarajan, N., Martins, A. S., Fritz, D. T., Garsetti, D., Lee, A. T., Hong, C. C., & Rogers, M. B. (2014). Bone morphogenetic protein-focused strategies to induce cytotoxicity in lung cancer cells. Anticancer Research, 34(5), 2095-2104.