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

doi:10.1007/s12672-018-0341-x

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 journal › Article › peer-review

24 Citations (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 language	English
Pages (from-to)	420-432
Number of pages	13
Journal	Hormones and Cancer
Volume	9
Issue number	6
DOIs	https://doi.org/10.1007/s12672-018-0341-x
Publication status	Published - Dec 1 2018

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s12672-018-0341-x

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Chang, T. C., Chin, Y. T., Nana, A. W., Wang, S. H., Liao, Y. M., Chen, Y. R., Shih, Y. J., Changou, C. A., Yang, Y. C. S., Wang, K., Whang-Peng, J., Wang, L. S., Stain, S. C., Shih, A., Lin, H. Y., Wu, C. H., & Davis, P. J. (2018). Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells: Mediation by EGFR Sialylation and PI3K Activation. Hormones and Cancer, 9(6), 420-432. https://doi.org/10.1007/s12672-018-0341-x

Chang, TC, Chin, YT, Nana, AW, Wang, SH, Liao, YM, Chen, YR, Shih, YJ, Changou, CA, Yang, YCS , Wang, K , Whang-Peng, J, Wang, LS, Stain, SC, Shih, A, Lin, HY, Wu, CH & Davis, PJ 2018, 'Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells: Mediation by EGFR Sialylation and PI3K Activation', Hormones and Cancer, vol. 9, no. 6, pp. 420-432. https://doi.org/10.1007/s12672-018-0341-x

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title = "Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells: Mediation by EGFR Sialylation and PI3K Activation",

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.",

author = "Chang, {Tung Cheng} and Chin, {Yu Tang} and Nana, {Andr{\'e} Wendindond{\'e}} and Wang, {Shwu Huey} and Liao, {Yu Min} and Chen, {Yi Ru} and Shih, {Ya Jung} and Changou, {Chun A.} and Yang, {Yu Chen Sh} and Kuan Wang and Jacqueline Whang-Peng and Wang, {Liang Shun} and Stain, {Steven C.} and Ai Shih and Lin, {Hung Yun} and Wu, {Chih Hsiung} and Davis, {Paul J.}",

note = "Publisher Copyright: {\textcopyright} 2018, The Author(s).",

year = "2018",

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doi = "10.1007/s12672-018-0341-x",

language = "English",

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T1 - Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells

T2 - Mediation by EGFR Sialylation and PI3K Activation

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.

PY - 2018/12/1

Y1 - 2018/12/1

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.

AB - 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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Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells: Mediation by EGFR Sialylation and PI3K Activation

Abstract

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