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; 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.

doi:10.1016/j.steroids.2016.03.006

Cited by 30 publications

(32 citation statements)

References 23 publications

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“…Knockdown of either HMGA2 or β-catenin enhanced resveratrol-induced COX-2 nuclear accumulation, which has been shown to be essential for integrin αvβ3-mediated resveratrol-induced apoptosis in cancer cells (Lin et al 2011b). Elsewhere, tetrac has been demonstrated to sensitize cancer cells to other anti-cancer agents or radiations (Rebbaa et al 2008, Lee et al 2016, Leith et al 2017, underlining the potential of this anti-cancer agent in therapeutic combination.…”

Section: Discussionmentioning

confidence: 99%

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Tetrac downregulates β-catenin and HMGA2 to promote the effect of resveratrol in colon cancer

Nana¹,

Chin²,

Lin³

et al. 2018

Endocrine-Related Cancer

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The molecular pathogenesis of colorectal cancer encompasses the activation of several oncogenic signaling pathways that include the Wnt/β-catenin pathway and the overexpression of high mobility group protein A2 (HMGA2). Resveratrol - the polyphenolic phytoalexin - binds to integrin αvβ3 to induce apoptosis in cancer cells cyclooxygenase 2 (COX-2) nuclear accumulation and p53-dependent apoptosis. Tetraiodothyroacetic acid (tetrac) is a de-aminated derivative of l-thyroxine (T), which - in contrast to the parental hormone - impairs cancer cell proliferation. In the current study, we found that tetrac promoted resveratrol-induced anti-proliferation in colon cancer cell lines, in primary cultures of colon cancer cells, and The mechanisms implicated in this action involved the downregulation of nuclear β-catenin and HMGA2, which are capable of compromising resveratrol-induced COX-2 nuclear translocation. Silencing of either β-catenin or HMGA2 promoted resveratrol-induced anti-proliferation and COX-2 nuclear accumulation which is essential for integrin αvβ3-mediated-resveratrol-induced apoptosis in cancer cells. Concurrently, tetrac enhanced nuclear abundance of chibby family member 1, the nuclear β-catenin antagonist, which may further compromise the nuclear β-catenin-dependent gene expression and proliferation. Taken together, these results suggest that tetrac targets β-catenin and HMGA2 to promote resveratrol-induced-anti-proliferation in colon cancers, highlighting its potential in anti-cancer combination therapy.

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Section: Discussionmentioning

confidence: 99%

“…Among such tetrac-regulated genes is CBY1, whose gene product is chibby family member 1, the nuclear β-catenin antagonist mentioned above (Glinskii et al 2009, Lin et al 2016b. Additionally, tetrac enhances the therapeutic potential of other anti-cancer agents (Lin et al 2011a, Lee et al 2016, Leith et al 2017.…”

Section: Introductionmentioning

confidence: 99%

Tetrac downregulates β-catenin and HMGA2 to promote the effect of resveratrol in colon cancer

Nana¹,

Chin²,

Lin³

et al. 2018

Endocrine-Related Cancer

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“…In addition to TRβ1 and TRα, another binding site of thyroid hormone is the cell surface integrin α v β 3 . Physiologic concentrations of thyroid hormones ( l ‐thyroxine (T 4 ) and 3,5,3‐triiodo‐ l ‐thyronine (T 3) ) bind to an integrin α v β 3 receptor on the plasma membrane, and, in vitro , stimulate the growth of various tumor cell lines, including glioma cells, medullary thyroid and papillary thyroid cancer cells, lung cancer cells, breast cancer cells, colorectal cancer cells, pancreatic cancer carcinoma, renal cell cancer cells, and ovarian cancer cells . The growth of tumor cells promoted by thyroid hormone is dependent on activated ERK1/2, and an inhibitor of ERK1/2, PD 98059, inhibits the proliferative activity of the hormone.…”

Section: Steroid Hormonesmentioning

confidence: 99%

“…The binding and activation of ERK1/2 by thyroid hormone can be suppressed by RGD peptide. The thyroid hormone receptor contains different binding domains on integrin α v β 3 : one binds both T 4 and T 3 , and the other is specific for T 3 ; the two sites have distinct roles in governing signal transduction pathways and cell functions . Nongenomically, T 3 activates the phosphatidylinositol 3‐kinase (PI3K) cascade via integrin α v β 3 binding, but T 4 does not activate PI3K by the same signal transduction pathway.…”

Section: Steroid Hormonesmentioning

confidence: 99%

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Mechanisms of action of nonpeptide hormones on resveratrol‐induced antiproliferation of cancer cells

Lin

Hsieh

Cheng

et al. 2017

Annals of the New York Academy of Sciences

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Nonpeptide hormones, such as thyroid hormone, dihydrotestosterone, and estrogen, have been shown to stimulate cancer proliferation via different mechanisms. Aside from their cytosolic or membrane-bound receptors, there are receptors on integrin α β for nonpeptide hormones. Interaction between hormones and integrin α β can induce signal transduction and eventually stimulate cancer cell proliferation. Resveratrol induces inducible COX-2-dependent antiproliferation via integrin α β . Resveratrol and hormone-induced signals are both transduced by activated extracellular-regulated kinases 1 and 2 (ERK1/2); however, hormones promote cell proliferation, while resveratrol induces antiproliferation in cancer cells. Hormones inhibit resveratrol-stimulated phosphorylation of p53 on Ser15, resveratrol-induced nuclear COX-2 accumulation, and formation of p53-COX-2 nuclear complexes. Subsequently, hormones impair resveratrol-induced COX-2-/p53-dependent gene expression. The inhibitory effects of hormones on resveratrol action can be blocked by different antagonists of specific nonpeptide hormone receptors but not integrin α β blockers. Results suggest that nonpeptide hormones inhibit resveratrol-induced antiproliferation in cancer cells downstream of the interaction between ligand and receptor and ERK1/2 activation to interfere with nuclear COX-2 accumulation. Thus, the surface receptor sites for resveratrol and nonpeptide hormones are distinct and can induce discrete ERK1/2-dependent downstream antiproliferation biological activities. It also indicates the complex pathways by which antiproliferation is induced by resveratrol in various physiological hormonal environments. .

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Thyroid Hormone, Cancer, and Apoptosis

Lin

Chin

Yang

et al. 2016

Comprehensive Physiology

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Thyroid hormones play important roles in regulating normal metabolism, development, and growth. They also stimulate cancer cell proliferation. Their metabolic and developmental effects and growth effects in normal tissues are mediated primarily by nuclear hormone receptors. A cell surface receptor for the hormone on integrin [alpha]vβ3 is the initiation site for effects on tumor cells. Clinical hypothyroidism may retard cancer growth, and hyperthyroidism was recently linked to the prevalence of certain cancers. Local levels of thyroid hormones are controlled through activation and deactivation of iodothyronine deiodinases in different organs. The relative activities of different deiodinases that exist in tissues or organs also affect the progression and development of specific types of cancers. In this review, the effects of thyroid hormone on signaling pathways in breast, brain, liver, thyroid, and colon cancers are discussed. The importance of nuclear thyroid hormone receptor isoforms and of the hormone receptor on the extracellular domain of integrin [alpha]vβ3 as potential cancer risk factors and therapeutic targets are addressed. We analyze the intracellular signaling pathways activated by thyroid hormones in cancer progression in hyperthyroidism or at physiological concentrations in the euthyroid state. Determining how to utilize the deaminated thyroid hormone analog (tetrac), and its nanoparticulate derivative to reduce risks of cancer progression, enhance therapeutic outcomes, and prevent cancer recurrence is also deliberated. © 2016 American Physiological Society. Compr Physiol 6:1221-1237, 2016.

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

Cited by 30 publications

References 23 publications

Tetrac downregulates β-catenin and HMGA2 to promote the effect of resveratrol in colon cancer

Tetrac downregulates β-catenin and HMGA2 to promote the effect of resveratrol in colon cancer

Mechanisms of action of nonpeptide hormones on resveratrol‐induced antiproliferation of cancer cells

Thyroid Hormone, Cancer, and Apoptosis

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