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Open Access 01-12-2018 | Original Paper

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

Authors: 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

Published in: Discover Oncology | Issue 6/2018

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.

Paria BC, Das SK, Mead RA, Dey SK (1994) Expression of epidermal growth factor receptor in the preimplantation uterus and blastocyst of the western spotted skunk. Biol Reprod 51(2):205–213CrossRef

Spano JP, Fagard R, Soria JC, Rixe O, Khayat D and Milano G (2005) Epidermal growth factor receptor signaling in colorectal cancer: preclinical data and therapeutic perspectives. Ann Oncol 16(2):189–194CrossRef

Kuramochi H, Nakajima G, Kaneko Y, Nakamura A, Inoue Y, Yamamoto M, Hayashi K (2012) Amphiregulin and Epiregulin mRNA expression in primary colorectal cancer and corresponding liver metastases. BMC Cancer 12:88CrossRef

Kanwar SS, Nautiyal J, Majumdar AP (2010) EGFR(S) inhibitors in the treatment of gastro-intestinal cancers: what's new? Curr Drug Targets 11(6):682–698CrossRef

Hu T, Li C (2010) Convergence between Wnt-beta-catenin and EGFR signaling in cancer. Mol Cancer 9:236CrossRef

Barbolina MV, Burkhalter RJ, Stack MS (2011) Diverse mechanisms for activation of Wnt signalling in the ovarian tumour microenvironment. Biochem J 437(1):1–12CrossRef

Shitoh K, Koinuma K, Furukawa T, Okada M, Nagai H (2004) Mutation of beta-catenin does not coexist with K-ras mutation in colorectal tumorigenesis. Dig Dis Sci 49(10):1631–1633CrossRef

Conlin A, Smith G, Carey FA, Wolf CR, Steele RJ (2005) The prognostic significance of K-ras, p53, and APC mutations in colorectal carcinoma. Gut 54(9):1283–1286CrossRef

Li J, Kleeff J, Giese N, Buchler MW, Korc M, Friess H (2004) Gefitinib ('Iressa', ZD1839), a selective epidermal growth factor receptor tyrosine kinase inhibitor, inhibits pancreatic cancer cell growth, invasion, and colony formation. Int J Oncol 25(1):203–210PubMed

10.

Park JJ, Yi JY, Jin YB, Lee YJ, Lee JS, Lee YS, Ko YG, Lee M (2012) Sialylation of epidermal growth factor receptor regulates receptor activity and chemosensitivity to gefitinib in colon cancer cells. Biochem Pharmacol 83(7):849–857CrossRef

11.

Janmaat ML, Giaccone G (2003) Small-molecule epidermal growth factor receptor tyrosine kinase inhibitors. Oncologist 8(6):576–586CrossRef

12.

Chen J, Bi H, Hou J, Zhang X, Zhang C, Yue L, Wen X, Liu D, Shi H, Yuan J, Liu J, Liu B (2013) Atorvastatin overcomes gefitinib resistance in KRAS mutant human non-small cell lung carcinoma cells. Cell Death Dis 4:e814CrossRef

13.

Li H, Schmid-Bindert G, Wang D, Zhao Y, Yang X, Su B, Zhou C (2011) Blocking the PI3K/AKT and MEK/ERK signaling pathways can overcome gefitinib-resistance in non-small cell lung cancer cell lines. Adv Med Sci 56(2):275–284CrossRef

14.

Dragowska WH, Weppler SA, Qadir MA, Wong LY, Franssen Y, Baker JH, Kapanen AI, Kierkels GJ, Masin D, Minchinton AI, Gelmon KA, Bally MB (2011) The combination of gefitinib and RAD001 inhibits growth of HER2 overexpressing breast cancer cells and tumors irrespective of trastuzumab sensitivity. BMC Cancer 11:420CrossRef

15.

Pao W, Wang TY, Riely GJ, Miller VA, Pan Q, Ladanyi M, Zakowski MF, Heelan RT, Kris MG, Varmus HE (2005) KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2(1):e17CrossRef

16.

Ono M, Kuwano M (2006) Molecular mechanisms of epidermal growth factor receptor (EGFR) activation and response to gefitinib and other EGFR-targeting drugs. Clin Cancer Res 12(24):7242–7251CrossRef

17.

Zhang X, Nagahara H, Mimori K, Inoue H, Sawada T, Ohira M, Hirakawa K, Mori M (2008) Mutations of epidermal growth factor receptor in colon cancer indicate susceptibility or resistance to gefitinib. Oncol Rep 19(6):1541–1544PubMed

18.

Song J, Zhu J, Zhao Q, Tian B (2015) Gefitinib causes growth arrest and inhibition of metastasis in human chondrosarcoma cells. J BUON 20(3):894–901PubMed

19.

Tebbutt N, Pedersen MW, Johns TG (2013) Targeting the ERBB family in cancer: couples therapy. Nat Rev Cancer 13(9):663–673CrossRef

20.

Toda D, Ota T, Tsukuda K, Watanabe K, Fujiyama T, Murakami M, Naito M, Shimizu N (2006) Gefitinib decreases the synthesis of matrix metalloproteinase and the adhesion to extracellular matrix proteins of colon cancer cells. Anticancer Res 26(1A):129–134PubMed

21.

Koizumi F, Kanzawa F, Ueda Y, Koh Y, Tsukiyama S, Taguchi F, Tamura T, Saijo N, Nishio K (2004) Synergistic interaction between the EGFR tyrosine kinase inhibitor gefitinib (“Iressa”) and the DNA topoisomerase I inhibitor CPT-11 (irinotecan) in human colorectal cancer cells. Int J Cancer 108(3):464–472CrossRef

22.

Giaccone G, Gonzalez-Larriba JL, van Oosterom AT, Alfonso R, Smit EF, Martens M, Peters GJ, van der Vijgh WJ, Smith R, Averbuch S, Fandi A (2004) Combination therapy with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, gemcitabine and cisplatin in patients with advanced solid tumors. Ann Oncol 15(5):831–838CrossRef

23.

Lin HY, Glinsky GV, Mousa SA, Davis PJ (2015) Thyroid hormone and anti-apoptosis in tumor cells. Oncotarget 6(17):14735–14743CrossRef

24.

Davis PJ, Glinsky GV, Lin HY, Leith JT, Hercbergs A, Tang HY, Ashur-Fabian O, Incerpi S, Mousa SA (2014) Cancer cell gene expression modulated from plasma membrane integrin αvβ3 by thyroid hormone and nanoparticulate tetrac. Front Endocrinol 5:240

25.

Glinskii AB, Glinsky GV, Lin HY, Tang HY, Sun M, Davis FB, Luidens MK, Mousa SA, Hercbergs AH, Davis PJ (2009) Modification of survival pathway gene expression in human breast cancer cells by tetraiodothyroacetic acid (tetrac). Cell Cycle 8(21):3562–3570CrossRef

26.

Lin HY, Landersdorfer CB, London D, Meng R, Lim CU, Lin C, Lin S, Tang HY, Brown D, Van Scoy B, Kulawy R, Queimado L, Drusano GL, Louie A, Davis FB, Mousa SA et al (2011) Pharmacodynamic modeling of anti-cancer activity of tetraiodothyroacetic acid in a perfused cell culture system. PLoS Comput Biol 7(2):e1001073CrossRef

27.

Yalcin M, Dyskin E, Lansing L, Bharali DJ, Mousa SS, Bridoux A, Hercbergs AH, Lin HY, Davis FB, Glinsky GV, Glinskii A, Ma J, Davis PJ, Mousa SA (2010) Tetraiodothyroacetic acid (tetrac) and nanoparticulate tetrac arrest growth of medullary carcinoma of the thyroid. J Clin Endocrinol Metab 95(4):1972–1980CrossRef

28.

Blanke CD (2005) Gefitinib in colorectal cancer: if wishes were horses. J Clin Oncol 23(24):5446–5449CrossRef

29.

Lin HY, Chin YT, Yang YC, Lai HY, Wang-Peng J, Liu LF, Tang HY, Davis PJ (2016) Thyroid hormone, cancer, and apoptosis. Compr Physiol 6(3):1221–1237CrossRef

30.

Janmaat ML, Rodriguez JA, Gallegos-Ruiz M, Kruyt FA, Giaccone G (2006) Enhanced cytotoxicity induced by gefitinib and specific inhibitors of the Ras or phosphatidyl inositol-3 kinase pathways in non-small cell lung cancer cells. Int J Cancer 118(1):209–214CrossRef

31.

Yuan HH, Han Y, Bian WX, Liu L, Bai YX (2012) The effect of monoclonal antibody cetuximab (C225) in combination with tyrosine kinase inhibitor gefitinib (ZD1839) on colon cancer cell lines. Pathology 44(6):547–551CrossRef

32.

Davis PJ, Goglia F, Leonard JL (2016) Nongenomic actions of thyroid hormone. Nat Rev Endocrinol 12(2):111–121CrossRef

33.

Baba Y, Fujii M, Tokumaru Y, Kato Y (2012) Present and future of EGFR inhibitors for head and neck squamous cell Cancer. J Oncol 2012:986725CrossRef

34.

Matsuo M, Sakurai H, Ueno Y, Ohtani O, Saiki I (2006) Activation of MEK/ERK and PI3K/Akt pathways by fibronectin requires integrin αv-mediated ADAM activity in hepatocellular carcinoma: a novel functional target for gefitinib. Cancer Sci 97(2):155–162CrossRef

35.

Liu Z, Klominek J (2004) Inhibition of proliferation, migration, and matrix metalloprotease production in malignant mesothelioma cells by tyrosine kinase inhibitors. Neoplasia 6(6):705–712CrossRef

36.

Matsuo M, Sakurai H, Saiki I (2003) ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, shows antimetastatic activity using a hepatocellular carcinoma model. Mol Cancer Ther 2(6):557–561PubMed

Title: Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells: Mediation by EGFR Sialylation and PI3K Activation
Authors: 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
Publication date: 01-12-2018
Publisher: Springer US
Published in: Discover Oncology / Issue 6/2018
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI: https://doi.org/10.1007/s12672-018-0341-x

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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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