Inhibition of pituitary tumor-transforming gene-1 in thyroid cancer cells by drugs that decrease specificity proteins

Sudhakar Chintharlapalli, Sabitha Papineni, Syng Ook Lee, Ping Lei, Un Ho Jin, Steven I. Sherman, Libero Santarpia, Stephen Safe

Research output: Contribution to journalArticle

Abstract

Methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate (CDODA-Me) and the corresponding 2-trifluoromethyl analog (CF3DODA-Me) are derived synthetically from the triterpenoid glycyrrhetinic acid, a major component of licorice. CDODA-Me and CF3DODA-Me inhibited growth of highly invasive ARO, DRO, K-18, and HTh-74 thyroid cancer cells and this was due, in part, to decreased expression of specificity protein (Sp) transcription factors Sp1, Sp3, and Sp4 that are overexpressed in these cells. CDODA-Me and CF3DODA-Me also decreased expression of Sp-dependent genes, such as survivin and vascular endothelial growth factor (VEGF), and induced apoptosis. In addition, pituitary tumor-transforming gene-1 (PTTG-1) protein and mRNA levels were also decreased in thyroid cancer cells treated with CDODA-Me or CF3DODA-Me and this was accompanied by decreased expression of PTTG-1-dependent c-Myc and fibroblast growth factor-2 (FGF-2) genes. RNA interference studies against Sp1, Sp3, and Sp4 proteins showed that in thyroid cancer cells, PTTG-1 was an Sp-dependent gene. This study demonstrates for the first time that drugs, such as CDODA-Me and CF3DODA-Me, that decrease Sp protein expression also downregulate PTTG-1 in thyroid cancer cells and therefore have potential for clinical treatment of thyroid cancer and other endocrine neoplasias where PTTG-1 is a major pro-oncogenic factor.

Original languageEnglish
Pages (from-to)655-667
Number of pages13
JournalMolecular Carcinogenesis
Volume50
Issue number9
DOIs
Publication statusPublished - Sep 2011

Fingerprint

Pituitary Neoplasms
Oncogenes
Thyroid Neoplasms
Pharmaceutical Preparations
Proteins
Sp Transcription Factors
Securin
Glycyrrhetinic Acid
Glycyrrhiza
Fibroblast Growth Factor 2
RNA Interference
Vascular Endothelial Growth Factor A
Down-Regulation
methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate
Apoptosis
Messenger RNA
Growth
Genes
Neoplasms

Keywords

  • Anticancer agents
  • PTTG-1
  • Sp proteins
  • Thyroid cancer

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

Chintharlapalli, S., Papineni, S., Lee, S. O., Lei, P., Jin, U. H., Sherman, S. I., ... Safe, S. (2011). Inhibition of pituitary tumor-transforming gene-1 in thyroid cancer cells by drugs that decrease specificity proteins. Molecular Carcinogenesis, 50(9), 655-667. https://doi.org/10.1002/mc.20738

Inhibition of pituitary tumor-transforming gene-1 in thyroid cancer cells by drugs that decrease specificity proteins. / Chintharlapalli, Sudhakar; Papineni, Sabitha; Lee, Syng Ook; Lei, Ping; Jin, Un Ho; Sherman, Steven I.; Santarpia, Libero; Safe, Stephen.

In: Molecular Carcinogenesis, Vol. 50, No. 9, 09.2011, p. 655-667.

Research output: Contribution to journalArticle

Chintharlapalli, Sudhakar ; Papineni, Sabitha ; Lee, Syng Ook ; Lei, Ping ; Jin, Un Ho ; Sherman, Steven I. ; Santarpia, Libero ; Safe, Stephen. / Inhibition of pituitary tumor-transforming gene-1 in thyroid cancer cells by drugs that decrease specificity proteins. In: Molecular Carcinogenesis. 2011 ; Vol. 50, No. 9. pp. 655-667.
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