2. Academic Validation
  3. Tetrac and NDAT Induce Anti-proliferation via Integrin αvβ3 in Colorectal Cancers With Different K-RAS Status

Tetrac and NDAT Induce Anti-proliferation via Integrin αvβ3 in Colorectal Cancers With Different K-RAS Status

  • Front Endocrinol (Lausanne). 2019 Mar 12;10:130. doi: 10.3389/fendo.2019.00130.
Yu-Tang Chin 1 2,  Zong-Rong He 3 4,  Chi-Long Chen 5,  Hsiao-Ching Chu 6,  Yih Ho 1 7,  Po-Yu Su 8,  Yu-Chen S H Yang 9,  Kuan Wang 1 8,  Ya-Jung Shih 1 8,  Yi-Ru Chen 1 8,  Jens Z Pedersen 10,  Sandra Incerpi 11,  André Wendindondé Nana 12,  Heng-Yuan Tang 13,  Hung-Yun Lin 1 12 13 14 15,  Shaker A Mousa 13,  Paul J Davis 13 16,  Jacqueline Whang-Peng 1 2 12
Affiliations

Affiliations

  • 1 Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
  • 2 Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
  • 3 Department of Pediatrics, E-Da Hospital, Kaohsiung, Taiwan.
  • 4 School of Medicine, I-Shou University, Kaohsiung, Taiwan.
  • 5 School of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 6 Division of Medical Imaging, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan.
  • 7 School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
  • 8 Graduate Institute of Nanomedicine and Medical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
  • 9 Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan.
  • 10 Department of Biology, University of Rome Tor Vergata, Rome, Italy.
  • 11 Department of Sciences, Roma Tre University, Rome, Italy.
  • 12 Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
  • 13 Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, United States.
  • 14 TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan.
  • 15 Traditional Herbal Medicine Research Center of Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
  • 16 Department of Medicine, Albany Medical College, Albany, NY, United States.
PMID: 30915033 DOI: 10.3389/fendo.2019.00130
Abstract

Colorectal Cancer is a serious medical problem in Taiwan. New, effective therapeutic approaches are needed. The selection of promising Anticancer drugs and the transition from pre-clinical investigations to clinical trials are often challenging. The deaminated thyroid hormone analog (tetraiodothyroacetic acid, tetrac) and its nanoparticulate analog (NDAT) have been shown to have anti-proliferative activity in vitro and in xenograft model of different neoplasms, including colorectal cancers. However, mechanisms involved in tetrac- and NDAT-induced anti-proliferation in colorectal cancers are incompletely understood. We have investigated possible mechanisms of tetrac and NDAT action in colorectal Cancer cells, using a perfusion bellows Cell Culture system that allows efficient, large-scale screening for mechanisms of drug actions on tumor cells. Although Integrin αvβ3 in K-Ras wild type colorectal Cancer HT-29 cells was far less than that in K-Ras mutant HCT116 cells, HT-29 was more sensitive to both tetrac and NDAT. Results also indicate that both tetrac and NDAT bind to tumor cell surface Integrin αvβ3, and the agents may have different mechanisms of anti-proliferation in colorectal Cancer cells. K-Ras status appears to play an important role in drug resistance that may be encountered in treatment with this drug combination.

Keywords

NDAT; anticancer; colorectal cancer cells; integrin αvβ3; perfusion bellows cell culture system; phosphoERK1/2; tetrac.

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