The combination of tetraiodothyroacetic acid and cetuximab inhibits cell proliferation in colorectal cancers with different K-ras status

Yee Shin Lee, Yu Tang Chin, Yu Chen S H Yang, Po Li Wei, Han Chung Wu, Ai Shih, Yueh Tong Lu, Jens Z. Pedersen, Sandra Incerpi, Leroy F. Liu, Hung Yun Lin, Paul J. Davis

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Thyroid hormone induces cancer cell proliferation through its cell surface receptor integrin αvβ3. Acting via integrin αvβ3, the deaminated T4 analog tetraiodothyroacetic acid (tetrac), and its nanoparticle formulation nano-diamino-tetrac (NDAT) could inhibit cell proliferation and xenograft growth. In this study, we investigated the T4 effects on proliferation in colorectal cancer cell lines based on the proliferation marker expressions at both mRNA and protein levels. The effects of tetrac/NDAT, the monoclonal anti-EGFR antibody cetuximab, and their combinations on colorectal cancer cell proliferation were examined according to the relevant gene expression profiles and cell count analysis. The results showed that T4 significantly enhanced PCNA, Cyclin D1 and c-Myc levels in both K-ras wild type HT-29 and mutant HCT 116 cells. In HCT 116 cells, the combination of NDAT and cetuximab significantly suppressed the mRNA expressions of proliferative genes PCNA, Cyclin D1, c-Myc and RRM2 raised by T4 compared to cetuximab alone. In addition, T4-suppressed mRNA expressions of pro-apoptotic genes p53 and RRM2B could be significantly elevated by the combination of NDAT and cetuximab compared to cetuximab alone. In the K-ras mutant HCT 116 cells, but not in the K-ras wild type COLO 205 cells, the combinations of tetrac/NDAT and cetuximab significantly reduced cell proliferation compared to cetuximab alone. In conclusion, T4 promoted colorectal cancer cell proliferation which could be repressed by tetrac and NDAT. The combinations of tetrac/NDAT and cetuximab potentiated cetuximab actions in K-ras mutant colorectal cancer cells.

Original languageEnglish
Pages (from-to)63-70
JournalSteroids
DOIs
Publication statusPublished - 2016

Fingerprint

Cell proliferation
Colorectal Neoplasms
Cell Proliferation
HCT116 Cells
Cyclin D1
Proliferating Cell Nuclear Antigen
Integrins
Messenger RNA
tetraiodothyroacetic acid
Cetuximab
Genes
Cells
bcl-1 Genes
p53 Genes
Cell Surface Receptors
Thyroid Hormones
Transcriptome
Heterografts
Gene expression
Nanoparticles

Keywords

  • Cetuximab
  • Colorectal cancer
  • NDAT
  • Tetrac
  • Thyroid hormone

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Molecular Biology
  • Organic Chemistry
  • Pharmacology

Cite this

The combination of tetraiodothyroacetic acid and cetuximab inhibits cell proliferation in colorectal cancers with different K-ras status. / Lee, Yee Shin; Chin, Yu Tang; Yang, Yu Chen S H; Wei, Po Li; Wu, Han Chung; Shih, Ai; Lu, Yueh Tong; Pedersen, Jens Z.; Incerpi, Sandra; Liu, Leroy F.; Lin, Hung Yun; Davis, Paul J.

In: Steroids, 2016, p. 63-70.

Research output: Contribution to journalArticle

Lee, Yee Shin ; Chin, Yu Tang ; Yang, Yu Chen S H ; Wei, Po Li ; Wu, Han Chung ; Shih, Ai ; Lu, Yueh Tong ; Pedersen, Jens Z. ; Incerpi, Sandra ; Liu, Leroy F. ; Lin, Hung Yun ; Davis, Paul J. / The combination of tetraiodothyroacetic acid and cetuximab inhibits cell proliferation in colorectal cancers with different K-ras status. In: Steroids. 2016 ; pp. 63-70.
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abstract = "Thyroid hormone induces cancer cell proliferation through its cell surface receptor integrin αvβ3. Acting via integrin αvβ3, the deaminated T4 analog tetraiodothyroacetic acid (tetrac), and its nanoparticle formulation nano-diamino-tetrac (NDAT) could inhibit cell proliferation and xenograft growth. In this study, we investigated the T4 effects on proliferation in colorectal cancer cell lines based on the proliferation marker expressions at both mRNA and protein levels. The effects of tetrac/NDAT, the monoclonal anti-EGFR antibody cetuximab, and their combinations on colorectal cancer cell proliferation were examined according to the relevant gene expression profiles and cell count analysis. The results showed that T4 significantly enhanced PCNA, Cyclin D1 and c-Myc levels in both K-ras wild type HT-29 and mutant HCT 116 cells. In HCT 116 cells, the combination of NDAT and cetuximab significantly suppressed the mRNA expressions of proliferative genes PCNA, Cyclin D1, c-Myc and RRM2 raised by T4 compared to cetuximab alone. In addition, T4-suppressed mRNA expressions of pro-apoptotic genes p53 and RRM2B could be significantly elevated by the combination of NDAT and cetuximab compared to cetuximab alone. In the K-ras mutant HCT 116 cells, but not in the K-ras wild type COLO 205 cells, the combinations of tetrac/NDAT and cetuximab significantly reduced cell proliferation compared to cetuximab alone. In conclusion, T4 promoted colorectal cancer cell proliferation which could be repressed by tetrac and NDAT. The combinations of tetrac/NDAT and cetuximab potentiated cetuximab actions in K-ras mutant colorectal cancer cells.",
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T1 - The combination of tetraiodothyroacetic acid and cetuximab inhibits cell proliferation in colorectal cancers with different K-ras status

AU - Lee, Yee Shin

AU - Chin, Yu Tang

AU - Yang, Yu Chen S H

AU - Wei, Po Li

AU - Wu, Han Chung

AU - Shih, Ai

AU - Lu, Yueh Tong

AU - Pedersen, Jens Z.

AU - Incerpi, Sandra

AU - Liu, Leroy F.

AU - Lin, Hung Yun

AU - Davis, Paul J.

PY - 2016

Y1 - 2016

N2 - Thyroid hormone induces cancer cell proliferation through its cell surface receptor integrin αvβ3. Acting via integrin αvβ3, the deaminated T4 analog tetraiodothyroacetic acid (tetrac), and its nanoparticle formulation nano-diamino-tetrac (NDAT) could inhibit cell proliferation and xenograft growth. In this study, we investigated the T4 effects on proliferation in colorectal cancer cell lines based on the proliferation marker expressions at both mRNA and protein levels. The effects of tetrac/NDAT, the monoclonal anti-EGFR antibody cetuximab, and their combinations on colorectal cancer cell proliferation were examined according to the relevant gene expression profiles and cell count analysis. The results showed that T4 significantly enhanced PCNA, Cyclin D1 and c-Myc levels in both K-ras wild type HT-29 and mutant HCT 116 cells. In HCT 116 cells, the combination of NDAT and cetuximab significantly suppressed the mRNA expressions of proliferative genes PCNA, Cyclin D1, c-Myc and RRM2 raised by T4 compared to cetuximab alone. In addition, T4-suppressed mRNA expressions of pro-apoptotic genes p53 and RRM2B could be significantly elevated by the combination of NDAT and cetuximab compared to cetuximab alone. In the K-ras mutant HCT 116 cells, but not in the K-ras wild type COLO 205 cells, the combinations of tetrac/NDAT and cetuximab significantly reduced cell proliferation compared to cetuximab alone. In conclusion, T4 promoted colorectal cancer cell proliferation which could be repressed by tetrac and NDAT. The combinations of tetrac/NDAT and cetuximab potentiated cetuximab actions in K-ras mutant colorectal cancer cells.

AB - Thyroid hormone induces cancer cell proliferation through its cell surface receptor integrin αvβ3. Acting via integrin αvβ3, the deaminated T4 analog tetraiodothyroacetic acid (tetrac), and its nanoparticle formulation nano-diamino-tetrac (NDAT) could inhibit cell proliferation and xenograft growth. In this study, we investigated the T4 effects on proliferation in colorectal cancer cell lines based on the proliferation marker expressions at both mRNA and protein levels. The effects of tetrac/NDAT, the monoclonal anti-EGFR antibody cetuximab, and their combinations on colorectal cancer cell proliferation were examined according to the relevant gene expression profiles and cell count analysis. The results showed that T4 significantly enhanced PCNA, Cyclin D1 and c-Myc levels in both K-ras wild type HT-29 and mutant HCT 116 cells. In HCT 116 cells, the combination of NDAT and cetuximab significantly suppressed the mRNA expressions of proliferative genes PCNA, Cyclin D1, c-Myc and RRM2 raised by T4 compared to cetuximab alone. In addition, T4-suppressed mRNA expressions of pro-apoptotic genes p53 and RRM2B could be significantly elevated by the combination of NDAT and cetuximab compared to cetuximab alone. In the K-ras mutant HCT 116 cells, but not in the K-ras wild type COLO 205 cells, the combinations of tetrac/NDAT and cetuximab significantly reduced cell proliferation compared to cetuximab alone. In conclusion, T4 promoted colorectal cancer cell proliferation which could be repressed by tetrac and NDAT. The combinations of tetrac/NDAT and cetuximab potentiated cetuximab actions in K-ras mutant colorectal cancer cells.

KW - Cetuximab

KW - Colorectal cancer

KW - NDAT

KW - Tetrac

KW - Thyroid hormone

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