Tetraiodothyroacetic acid and its nanoformulation inhibit thyroid hormone stimulation of non-small cell lung cancer cells in vitro and its growth in xenografts

Mousa S. A., Yalcin M., Bharali D. J., Meng R., Tang H., Lin H., ...More

LUNG CANCER, vol.76, no.1, pp.39-45, 2012 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 76 Issue: 1
  • Publication Date: 2012
  • Doi Number: 10.1016/j.lungcan.2011.10.003
  • Journal Name: LUNG CANCER
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.39-45
  • Keywords: Non-small cell lung cancer, Thyroid hormone, Tetrac, Tetrac nanoparticles, Angiogenesis, Cell surface integrin alpha v beta 3 receptor, Cancer, ACTIVATED PROTEIN-KINASE, SURFACE RECEPTOR, L-THYROXINE, INTEGRIN, HYPOTHYROIDISM, CARCINOMA, TETRAC, GLIOMA, 3,5,3'-TRIIODO-L-THYRONINE, PROLIFERATION
  • Bursa Uludag University Affiliated: Yes


Thyroid hormone stimulates cell proliferation of several types of cancers and stimulates cancer-relevant angiogenesis. In the present study, we investigated the proliferative effect of thyroid hormone and the anti-proliferative and anti-angiogenic action of its nano-derivative, tetrac-NP, on human non-small cell lung cancer (NSCLC) H1299 cells in vitro and in xenografts. The anti-proliferative activity of unmodified tetrac and tetrac-NP against human H1299 cells was determined in three models: (a) cultured H1299 cells in vitro, (b) tumor cell implants in the fertilized chick chorioallantoic membrane (CAM) system and (c) xenografts in the nude mouse. An integrin alpha v beta 3 antibody inhibited thyroid hormone-induced cell proliferation in vitro, as did unmodified tetrac and tetrac-NP. Pharmacologic inhibition of the mitogen-activated protein kinase pathway also blocked NSCLC cell proliferation in response to thyroid hormone. Tetrac and tetrac-NP arrested tumor growth and tumor-related angiogenesis in H1299 cells grown in the CAM model and both agents prevented chick embryo mortality. Xenografts of H1299 cells were established in nude mice (n = 8, treatment and control groups) and when tumor volumes reached 250-300 mm(3), tetrac (1 mg/kg) or tetrac-NP (1 mg tetrac as the nanoparticle/kg) were administered intraperitoneally every 2 days. Tetrac and tetrac-NP significantly suppressed tumor growth and angiogenesis. Thus, both tetrac and tetrac-NP effectively arrest human NSCLC tumor cell proliferation in vitro and in the CAM assay and in murine xenograft models. (C) 2011 Elsevier Ireland Ltd. All rights reserved.