Radiosensitization and production of DNA double-strand breaks in U87MG brain tumor cells induced by tetraiodothyroacetic acid (tetrac)

Hercbergs, Aleck; Lin, Hung Yun; Davis, Faith B.; Davis, Paul J.; Leith, John T.

doi:10.4161/cc.10.2.14641

Cited by 35 publications

(27 citation statements)

References 28 publications

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“…For instance, using tetraiodothyroacetic acid (tetrac) in combination with radiation can successfully produce DNA double-strand breaks and sensitizes the drug response of U87MG cell line. 39 The abrogation of PIK3CA or PIK3R1 also reduces proliferation, migration and invasion, since these two genes are frequently found to be mutated and overexpressed in GBM. 40 NFκB is also viewed as an important therapeutic target of GBM, which implicates IKKβ inhibitors in interfering with NFκB activation in order to prohibit the limitless replicative potential, tissue invasion interrelationships among GSK3b, BCL2L12 and BCL2L12A in glioblastoma, as shown in Figure 6.…”

Section: Discussionmentioning

confidence: 99%

GSK3β regulates Bcl2L12 and Bcl2L12A anti-apoptosis signaling in glioblastoma and is inhibited by LiCl

Chou

Chou²,

Lin³

et al. 2012

Cell Cycle

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Section: Discussionmentioning

confidence: 99%

GSK3β regulates Bcl2L12 and Bcl2L12A anti-apoptosis signaling in glioblastoma and is inhibited by LiCl

Chou

Chou²,

Lin³

et al. 2012

Cell Cycle

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“…Tetraiodothyroacetic acid (tetrac) and the newly developed tetrac-nanoparticle (tetrac NP) lack traditional agonist T 4 functions and selectively block T 3 /T 4 binding to the thyroid hormone receptor site on avb3 (18). These agents reduce cancer cell proliferation, migration, and angiogenesis in vitro and in animal models (18)(19)(20)(21) and induce apoptosis (22,23) and double-strand DNA breaks (24). The fact that integrin avb3 is overexpressed in a variety of cancer cell types (25) and the central role of the MAPK and PI3K cascades in many cancer cells (26,27) can support concerns that thyroid hormone may promote tumor cell proliferation in the clinical setting (7,18).…”

Section: Introductionmentioning

confidence: 99%

Thyroid Hormone Is a MAPK-Dependent Growth Factor for Human Myeloma Cells Acting via αvβ3 Integrin

Cohen

Ellis

Khoury

et al. 2011

Molecular Cancer Research

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Experimental and clinical observations suggest that thyroid hormone [L-thyroxine (T 4 ) and 3,5,30 -triiodo-Lthyronine (T 3 )] can support cancer cell proliferation. T 3 and T 4 promote both tumor cell division and angiogenesis by activating mitogen-activated protein kinase (MAPK) via binding to a hormone receptor on the avb3 integrin, overexpressed on many cancer cells. We have studied the responsiveness of several MM cell lines to T 3 and T 4 and characterized hormonal effects on cell survival, proliferation, and MAPK activation. Overnight T 3 (1-100 nmol/L) and T 4 (100 nmol/L) incubation enhanced, up to 50% (P < 0.002), MM cell viability (WST-1 assay) and increased cell proliferation by 30% to 60% (P < 0.01). Short exposure (10 minutes) to T 3 and T 4 increased MAPK activity by 2.5-to 3.5-fold (P < 0.03). Pharmacologic MAPK inhibition blocked the proliferative action of T 3 and T 4 . Antibodies to the integrin avb3 dimer and av and b3 monomers (but not b1) inhibited MAPK activation and subsequent cell proliferation in response to thyroid hormone, indicating dependence upon this integrin. Moreover, tetraiodothyroacetic acid (tetrac), a non-agonist T 4 analogue previously shown to selectively block T 3 /T 4 binding to avb3 receptor site, blocked induction of MAPK by the hormones in a dose-dependent manner. This demonstration of the role of thyroid hormones as growth factors for MM cells may offer novel therapeutic approaches. Mol Cancer Res; 9(10); 1385-94. Ó2011 AACR.

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“…A thyroid hormone on plasma membrane integrin v3 initiates the actions of the hormone and certain analogues on angiogenesis Davis et al, 2009), on tumor cell proliferation (Rebbaa, 2008;Yalcin, Bharali et al, 2010;Yalcin et al, 2010;Meng et al, 2011) and on cancer cell radiosensitivity Hercbergs et al, 2011). These effects are initiated nongenomically, i.e., are independent of the classical nuclear receptor for thyroid hormone (TR) (Cheng et al, 2010), and may have downstream intracellular consequences that involve specific protein trafficking (Cao et al, 2009) and modulation of expression of specific genes involved in cancer cell survival pathways.…”

Section: Introductionmentioning

confidence: 99%

Integrin-Mediated Actions of Thyroid Hormone Analogues on Tumor Cell Chemosensitivity, Integrin-Growth Factor Receptor Crosstalk and Inflammatory Gene Expression

Lin

Tang

Davis

et al. 2012

CCO

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Tetraiodothyroacetic acid (tetrac) and its nanoparticulate formulation induce apoptosis in cancer cells, oppose angiogenesis about xenografted human tumors and block cancer cell repair of double-stranded DNA breaks. These nongenomic actions of tetrac are initiated at a tetrac-thyroid hormone receptor on plasma membrane integrin v3. In this review, we examine additional anti-cancer activities of tetrac formulations at v3 and what is known about their mechanisms. These activities include 1) reversal of cancer cell chemoresistance (= induction of chemosensitization) and 2) disruption of crosstalk between v3 and nearby cell surface growth factor receptors. In addition, nanoparticulate tetrac 3) alters expression of differentially-regulated inflammation-relevant genes that may be important to inflammation-supported cancer. For example, the agent downregulates genes whose products mediate cytokine responses and upregulates suppressor of cytokine signaling, SOCS4. Such actions of tetrac formulations define a multi-target functional profile, although the activities of tetrac begin at a single anatomic plasma membrane receptor on integrin v3.

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Radiosensitization and production of DNA double-strand breaks in U87MG brain tumor cells induced by tetraiodothyroacetic acid (tetrac)

Cited by 35 publications

References 28 publications

GSK3β regulates Bcl2L12 and Bcl2L12A anti-apoptosis signaling in glioblastoma and is inhibited by LiCl

GSK3β regulates Bcl2L12 and Bcl2L12A anti-apoptosis signaling in glioblastoma and is inhibited by LiCl

Thyroid Hormone Is a MAPK-Dependent Growth Factor for Human Myeloma Cells Acting via αvβ3 Integrin

Integrin-Mediated Actions of Thyroid Hormone Analogues on Tumor Cell Chemosensitivity, Integrin-Growth Factor Receptor Crosstalk and Inflammatory Gene Expression

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