Actions of l-thyroxine and Nano-diamino-tetrac (Nanotetrac) on PD-L1 in cancer cells

Lin, Hung Yun; Chin, Yu Tang; Nana, André Wendindondé; Shih, Ya-Jung; Lai, Hsuan-Yu; Tang, Heng-Yuan; Leinung, Matthew C.; Mousa, Shaker A.; Davis, Paul J.

doi:10.1016/j.steroids.2016.05.006

Cited by 64 publications

(70 citation statements)

References 28 publications

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“…Finally, the PD-1 (programmed death-1)/PD-L1 (PD-ligand 1) immune checkpoint is affected by physiological concentrations of T 4 , in that the hormone stimulates expression in a variety of cell lines of the PD-L1 gene [50]. NDAT blocks this effect.…”

Section: Discussionmentioning

confidence: 99%

Nanoparticulate Tetrac Inhibits Growth and Vascularity of Glioblastoma Xenografts

et al. 2017

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Thyroid hormone as L-thyroxine (T4) stimulates proliferation of glioma cells in vitro and medical induction of hypothyroidism slows clinical growth of glioblastoma multiforme (GBM). The proliferative action of T4 on glioma cells is initiated nongenomically at a cell surface receptor for thyroid hormone on the extracellular domain of integrin αvβ3. Tetraiodothyroacetic acid (tetrac) is a thyroid hormone derivative that blocks T4 action at αvβ3 and has anticancer and anti-angiogenic activity. Tetrac has been covalently bonded via a linker to a nanoparticle (Nanotetrac, Nano-diamino-tetrac, NDAT) that increases the potency of tetrac and broadens the anticancer properties of the drug. In the present studies of human GBM xenografts in immunodeficient mice, NDAT administered daily for 10 days subcutaneously as 1 mg tetrac equivalent/kg reduced tumor xenograft weight at animal sacrifice by 50%, compared to untreated control lesions (p < 0.01). Histopathological analysis of tumors revealed a 95% loss of the vascularity of treated tumors compared to controls at 10 days (p < 0.001), without intratumoral hemorrhage. Up to 80% of tumor cells were necrotic in various microscopic fields (p < 0.001 vs. control tumors), an effect attributable to devascularization. There was substantial evidence of apoptosis in other fields (p < 0.001 vs. control tumors). Induction of apoptosis in cancer cells is a well-described quality of NDAT. In summary, systemic NDAT has been shown to be effective by multiple mechanisms in treatment of GBM xenografts.Electronic supplementary materialThe online version of this article (doi:10.1007/s12672-017-0293-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Nanoparticulate Tetrac Inhibits Growth and Vascularity of Glioblastoma Xenografts

et al. 2017

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“…Thyroid hormones induce tumor growth and angiogenesis via αvβ3-integrin [112,113]. On the basis of this concept, researchers have used tetrac to manufacture integrin-targeted NPs, which have recently shown promising results in preclinical studies [114,115].…”

Section: Non-rgd Integrin-targeted Ligandsmentioning

confidence: 99%

Targeting Integrins in Cancer Nanomedicine: Applications in Cancer Diagnosis and Therapy

Opadele

Onodera

et al. 2019

Cancers

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Due to advancements in nanotechnology, the application of nanosized materials (nanomaterials) in cancer diagnostics and therapeutics has become a leading area in cancer research. The decoration of nanomaterial surfaces with biological ligands is a major strategy for directing the actions of nanomaterials specifically to cancer cells. These ligands can bind to specific receptors on the cell surface and enable nanomaterials to actively target cancer cells. Integrins are one of the cell surface receptors that regulate the communication between cells and their microenvironment. Several integrins are overexpressed in many types of cancer cells and the tumor microvasculature and function in the mediation of various cellular events. Therefore, the surface modification of nanomaterials with integrin-specific ligands not only increases their binding affinity to cancer cells but also enhances the cellular uptake of nanomaterials through the intracellular trafficking of integrins. Moreover, the integrin-specific ligands themselves interfere with cancer migration and invasion by interacting with integrins, and this finding provides a novel direction for new treatment approaches in cancer nanomedicine. This article reviews the integrin-specific ligands that have been used in cancer nanomedicine and provides an overview of the recent progress in cancer diagnostics and therapeutic strategies involving the use of integrin-targeted nanomaterials.

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“…Nuclear proteins were extracted following the Thermo Scientific NE-PER Nuclear and Cytoplasmic Extraction Kit protocol (Thermo Scientific). The blotting technics are standard and have been described in several of our manuscripts (Chin et al 2015, Lin et al 2016a. Secondary antibodies were goat anti-rabbit IgG, rabbit anti-mouse IgG or rabbit anti-goat horseradish peroxidase, depending on the origin of the primary antibody.…”

Section: Immunoblottingmentioning

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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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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Actions of l-thyroxine and Nano-diamino-tetrac (Nanotetrac) on PD-L1 in cancer cells

Cited by 64 publications

References 28 publications

Nanoparticulate Tetrac Inhibits Growth and Vascularity of Glioblastoma Xenografts

Nanoparticulate Tetrac Inhibits Growth and Vascularity of Glioblastoma Xenografts

Targeting Integrins in Cancer Nanomedicine: Applications in Cancer Diagnosis and Therapy

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

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