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

Shaker A. Mousa, Murat Yalcin, Dhruba J. Bharali, Ran Meng, Heng Yuan Tang, Hung Yun Lin, Faith B. Davis, Paul J. Davis

Research output: Contribution to journalArticle

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Abstract

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 αvβ3 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 250-300mm 3, tetrac (1mg/kg) or tetrac-NP (1mg 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.

Original languageEnglish
Pages (from-to)39-45
Number of pages7
JournalLung Cancer
Volume76
Issue number1
DOIs
Publication statusPublished - Apr 2012
Externally publishedYes

Fingerprint

Thyroid Hormones
Heterografts
Non-Small Cell Lung Carcinoma
Growth
Nanoparticles
Chorioallantoic Membrane
Neoplasms
Cell Proliferation
Nude Mice
In Vitro Techniques
tetraiodothyroacetic acid
Chick Embryo
Mitogen-Activated Protein Kinases
Tumor Burden
Integrins
Cultured Cells

Keywords

  • Angiogenesis
  • Cancer
  • Cell surface integrin αvβ3 receptor
  • Non-small cell lung cancer
  • Tetrac
  • Tetrac nanoparticles
  • Thyroid hormone

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Tetraiodothyroacetic acid and its nanoformulation inhibit thyroid hormone stimulation of non-small cell lung cancer cells in vitro and its growth in xenografts. / Mousa, Shaker A.; Yalcin, Murat; Bharali, Dhruba J.; Meng, Ran; Tang, Heng Yuan; Lin, Hung Yun; Davis, Faith B.; Davis, Paul J.

In: Lung Cancer, Vol. 76, No. 1, 04.2012, p. 39-45.

Research output: Contribution to journalArticle

Mousa, Shaker A. ; Yalcin, Murat ; Bharali, Dhruba J. ; Meng, Ran ; Tang, Heng Yuan ; Lin, Hung Yun ; Davis, Faith B. ; Davis, Paul J. / Tetraiodothyroacetic acid and its nanoformulation inhibit thyroid hormone stimulation of non-small cell lung cancer cells in vitro and its growth in xenografts. In: Lung Cancer. 2012 ; Vol. 76, No. 1. pp. 39-45.
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AB - 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 αvβ3 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 250-300mm 3, tetrac (1mg/kg) or tetrac-NP (1mg 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.

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