Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells

Mediation by EGFR Sialylation and PI3K Activation

Tung Cheng Chang, Yu Tang Chin, André Wendindondé Nana, Shwu Huey Wang, Yu Min Liao, Yi Ru Chen, Ya Jung Shih, Chun A. Changou, Yu Chen Sh Yang, Kuan Wang, Jacqueline Whang-Peng, Liang Shun Wang, Steven C. Stain, Ai Shih, Hung Yun Lin, Chih Hsiung Wu, Paul J. Davis

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Drug resistance complicates the clinical use of gefitinib. Tetraiodothyroacetic acid (tetrac) and nano-diamino-tetrac (NDAT) have been shown in vitro and in xenografts to have antiproliferative/angiogenic properties and to potentiate antiproliferative activity of other anticancer agents. In the current study, we investigated the effects of NDAT on the anticancer activities of gefitinib in human colorectal cancer cells. β-Galactoside α-2,6-sialyltransferase 1 (ST6Gal1) catalyzes EGFR sialylation that is associated with gefitinib resistance in colorectal cancers, and this was also investigated. Gefitinib inhibited cell proliferation of HT-29 cells (K-ras wild-type), and NDAT significantly enhanced the antiproliferative action of gefitinib. Gefitinib inhibited cell proliferation of HCT116 cells (K-ras mutant) only in high concentration, and this was further enhanced by NDAT. NDAT enhancedd gefitinib-induced antiproliferation in gefitinib-resistant colorectal cancer cells by inhibiting ST6Gal1 activity and PI3K activation. Furthermore, NDAT enhanced gefitinib-induced anticancer activity additively in colorectal cancer HCT116 cell xenograft-bearing nude mice. Results suggest that NDAT may have an application with gefitinib as combination colorectal cancer therapy.

Original languageEnglish
JournalHormones and Cancer
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Phosphatidylinositol 3-Kinases
Colorectal Neoplasms
HCT116 Cells
Heterografts
Cell Proliferation
gefitinib
tetraiodothyroacetic acid
Sialyltransferases
Galactosides
HT29 Cells
Drug Resistance
Nude Mice
Antineoplastic Agents

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cancer Research

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Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells : Mediation by EGFR Sialylation and PI3K Activation. / Chang, Tung Cheng; Chin, Yu Tang; Nana, André Wendindondé; Wang, Shwu Huey; Liao, Yu Min; Chen, Yi Ru; Shih, Ya Jung; Changou, Chun A.; Yang, Yu Chen Sh; Wang, Kuan; Whang-Peng, Jacqueline; Wang, Liang Shun; Stain, Steven C.; Shih, Ai; Lin, Hung Yun; Wu, Chih Hsiung; Davis, Paul J.

In: Hormones and Cancer, 01.01.2018.

Research output: Contribution to journalArticle

Chang, Tung Cheng ; Chin, Yu Tang ; Nana, André Wendindondé ; Wang, Shwu Huey ; Liao, Yu Min ; Chen, Yi Ru ; Shih, Ya Jung ; Changou, Chun A. ; Yang, Yu Chen Sh ; Wang, Kuan ; Whang-Peng, Jacqueline ; Wang, Liang Shun ; Stain, Steven C. ; Shih, Ai ; Lin, Hung Yun ; Wu, Chih Hsiung ; Davis, Paul J. / Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells : Mediation by EGFR Sialylation and PI3K Activation. In: Hormones and Cancer. 2018.
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abstract = "Drug resistance complicates the clinical use of gefitinib. Tetraiodothyroacetic acid (tetrac) and nano-diamino-tetrac (NDAT) have been shown in vitro and in xenografts to have antiproliferative/angiogenic properties and to potentiate antiproliferative activity of other anticancer agents. In the current study, we investigated the effects of NDAT on the anticancer activities of gefitinib in human colorectal cancer cells. β-Galactoside α-2,6-sialyltransferase 1 (ST6Gal1) catalyzes EGFR sialylation that is associated with gefitinib resistance in colorectal cancers, and this was also investigated. Gefitinib inhibited cell proliferation of HT-29 cells (K-ras wild-type), and NDAT significantly enhanced the antiproliferative action of gefitinib. Gefitinib inhibited cell proliferation of HCT116 cells (K-ras mutant) only in high concentration, and this was further enhanced by NDAT. NDAT enhancedd gefitinib-induced antiproliferation in gefitinib-resistant colorectal cancer cells by inhibiting ST6Gal1 activity and PI3K activation. Furthermore, NDAT enhanced gefitinib-induced anticancer activity additively in colorectal cancer HCT116 cell xenograft-bearing nude mice. Results suggest that NDAT may have an application with gefitinib as combination colorectal cancer therapy.",
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AU - Chang, Tung Cheng

AU - Chin, Yu Tang

AU - Nana, André Wendindondé

AU - Wang, Shwu Huey

AU - Liao, Yu Min

AU - Chen, Yi Ru

AU - Shih, Ya Jung

AU - Changou, Chun A.

AU - Yang, Yu Chen Sh

AU - Wang, Kuan

AU - Whang-Peng, Jacqueline

AU - Wang, Liang Shun

AU - Stain, Steven C.

AU - Shih, Ai

AU - Lin, Hung Yun

AU - Wu, Chih Hsiung

AU - Davis, Paul J.

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N2 - Drug resistance complicates the clinical use of gefitinib. Tetraiodothyroacetic acid (tetrac) and nano-diamino-tetrac (NDAT) have been shown in vitro and in xenografts to have antiproliferative/angiogenic properties and to potentiate antiproliferative activity of other anticancer agents. In the current study, we investigated the effects of NDAT on the anticancer activities of gefitinib in human colorectal cancer cells. β-Galactoside α-2,6-sialyltransferase 1 (ST6Gal1) catalyzes EGFR sialylation that is associated with gefitinib resistance in colorectal cancers, and this was also investigated. Gefitinib inhibited cell proliferation of HT-29 cells (K-ras wild-type), and NDAT significantly enhanced the antiproliferative action of gefitinib. Gefitinib inhibited cell proliferation of HCT116 cells (K-ras mutant) only in high concentration, and this was further enhanced by NDAT. NDAT enhancedd gefitinib-induced antiproliferation in gefitinib-resistant colorectal cancer cells by inhibiting ST6Gal1 activity and PI3K activation. Furthermore, NDAT enhanced gefitinib-induced anticancer activity additively in colorectal cancer HCT116 cell xenograft-bearing nude mice. Results suggest that NDAT may have an application with gefitinib as combination colorectal cancer therapy.

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