Action of Low Calcemic 1 ,25-Dihydroxyvitamin D3 Analogue EB1089 in Head and Neck Squamous Cell Carcinoma

Prudencio, José; Akutsu, Naotake; Benlimame, Naciba; Wang, Taiqui; Bastien, Yolande; Lin, Roberto; Black, Martin J.; Alaoui‐Jamali, Moulay A.; White, John H.

doi:10.1093/jnci/93.10.745

Cited by 67 publications

(59 citation statements)

References 42 publications

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“…This is consistent with the identification of the VDRE in the fourth exon that is distant from the p53 binding site in the third intron (30). This is also consistent with the conclusion reached by a published study in squamous cell carcinoma (44). Furthermore the regulation is also likely to be independent of BRCA1 since the DNA element for this tumor suppressor is located in the promoter region (51).…”

Section: Discussionsupporting

confidence: 92%

See 1 more Smart Citation

G2/M Arrest by 1,25-Dihydroxyvitamin D3 in Ovarian Cancer Cells Mediated through the Induction of GADD45 via an Exonic Enhancer

Jiang

Fornace

et al. 2003

Journal of Biological Chemistry

120

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Vitamin D 3 (VD) 1 is a lipophilic hormone essential for normal bone structure and maintenance of serum calcium (1). VD action is mediated through the vitamin D receptor (VDR) (2), a member of the steroid/thyroid receptor superfamily of ligandregulated transcription factors (3-5). This superfamily includes receptors for steroids such as progesterone, androgens, estrogens, glucocorticoids, and mineralocorticoids; receptors for non-steroid hormones like vitamin D, thyroid hormones, alltrans-retinoic acid and 9-cis-retinoic acid; and orphan receptors for which the ligand is unknown. VDR and other non-steroid receptor members of the superfamily form heterodimers with the retinoid X receptor (RXR), the receptor for 9-cis-retinoic acid. In most cases, the VDR⅐RXR heterodimer binds VD response elements (VDREs) to mediate the biological activities of VD through transcriptional activation or repression of target genes containing VDREs in their regulatory sequence. In response to VD activation, the VDR recruits multiple coactivators, including members of the p160 steroid receptor coactivator family (6), which are associated with histone acetyltransferase activity, and the vitamin D receptor interacting proteins complex (7); the latter serves as a mediator between the VDR and RNA polymerase II (Pol II) complex.In addition to its well defined role in calcium homeostasis and bone cell metabolism, the active metabolite of VD, 1,25-dihydroxyvitamin D 3 (1,25VD), modulates cellular proliferation and differentiation of both normal and malignant cells (8). 1,25VD and its synthetic analogues can inhibit carcinogenesis in mouse skin (9, 10), decrease the size of transplanted sarcomas, reduce lung metastasis in mice (11), suppress the growth of human colonic cancer cell-derived xenografts in immunesuppressed mice (12), and increase cell differentiation and decrease proliferation of leukemia (13), breast cancer (14), and prostate cancer (15) cells. Studies in cancer cell lines have shown that 1,25VD causes cancer cells to accumulate in the G 1 phase of the cell cycle (15) or in the G 2 phase (16) or to undergo apoptosis (17,18). Genes that mediate each of these specific activities remain largely unidentified.Similar to breast and prostate cancers, ovarian cancer (OCa) mortality and incident rates are lower in countries within 20°o f the equator (19) where there is a high amount of sunlight. In the United States, women between the ages of 45 and 54 living in the north have 5 times the OCa mortality rate than women living in southern states (20,21). In the epidermis, sunlight controls the first step of 1,25VD synthesis, namely the photoconversion of 7-dehydrocholesterol to pre-vitamin D 3 . Exposure to sunlight, rather than food consumption, is the primary source of 1,25VD (22). The inverse correlation between sunlight exposure and OCa mortality indicates that decreased synthesis of 1,25VD may contribute to OCa initiation and/or progression. VDR has been found in rat ovaries by immunohistochemistry (23) and in hen ovaries by ligand bin...

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Section: Discussionsupporting

confidence: 92%

“…This shows that GADD45 induction by 1,25VD does not require new protein synthesis, thus identifying GADD45 as a primary target gene for 1,25VD in OCa cells. This is consistent with similar data in squamous cell carcinoma (44,45).…”

Section: 25vd Suppresses Oca Cell Growth and Induces Cell Cyclesupporting

confidence: 94%

G2/M Arrest by 1,25-Dihydroxyvitamin D3 in Ovarian Cancer Cells Mediated through the Induction of GADD45 via an Exonic Enhancer

Jiang

Fornace

et al. 2003

Journal of Biological Chemistry

120

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“…For in vivo pharmacokinetic studies in male, C57BL/6 mice (8 wk old), doses of either 0 or 2.5 g/kg (or 0.05 g/mouse or 120 pmol) 1,25(OH) 2D3, dissolved in sterile corn oil (5 l/g), were given ip on days 0, 2, 4, and 8 at 9 AM. The dose was based on a series of published reports, with doses ranging from 0.1 to 5 g/mouse or 0.25 to 5 g/kg for ip or oral administration, daily or every other day in mice (1,2,27,37,39,42,47,55). In humans, doses of 1,25(OH) 2D3 (0.5 g/kg or 38 g) furnished a similar clearance and exposure with minimal toxicity when used intermittently (8,38).…”

Section: Methodsmentioning

confidence: 99%

Temporal changes in tissue 1α,25-dihydroxyvitamin D₃, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)₂D₃treatment in mice

Chow

Quach

Vieth

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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, its natural active ligand, by directly regulating the calcium ion channel (TRPV6) and degradation enzyme (CYP24A1), and indirectly regulating the parathyroid hormone (PTH) for feedback regulation of the synthetic enzyme CYP27B1. Studies that examined the intricate relationships between plasma and tissue 1,25(OH) 2D3 levels and changes in VDR target genes and plasma calcium and PTH are virtually nonexistent. In this study, we investigated temporal correlations between tissue 1,25(OH) 2D3 concentrations and VDR target genes in ileum and kidney and plasma calcium and PTH concentrations in response to 1,25(OH) 2D3 treatment in mice (2.5 g/kg ip, singly or q2d ϫ 4). After a single ip dose, plasma 1,25(OH) 2D3 peaked at ϳ0.5 h and then decayed biexponentially, falling below basal levels after 24 h and then returning to baseline after 8 days. Upon repetitive ip dosing, plasma, ileal, renal, and bone 1,25(OH) 2D3 concentrations rose and decayed in unison. Temporal profiles showed increased expressions of ileal Cyp24a1 and renal Cyp24a1, Mdr1/P-gp, and VDR but decreased renal Cyp27b1 mRNA after a time delay in VDR activation. Increased plasma calcium and attenuated PTH levels and increased ileal and renal Trpv6 expression paralleled the changes in tissue 1,25(OH) 2D3 concentrations. Gene changes in the kidney were more sustained than those in intestine, but the magnitudes of change for Cyp24a1 and Trpv6 were lower than those in intestine. The data revealed that 1,25(OH) 2D3 equilibrates with tissues rapidly, and VDR target genes respond quickly to exogenously administered 1,25(OH) 2D3. Upon binding of 1,25(OH) 2 D 3 to VDR, the complex undergoes a conformational change and translocates to the nucleus to heterodimerize with the retinoid X receptor (RXR) (4, 32), followed by recruitment of coactivators before binding to vitamin D response elements (VDREs) in promoter regions of VDR-responsive genes to initiate gene transcription (19). One of the physiological roles of 1,25(OH) 2 D 3 is to increase plasma calcium levels through transactivation of the calcium ion channels [transient receptor potential cation channel subfamily V members 5 and 6 (TRPV5 and TRPV6)] in the kidney and intestine (46). It is known that calcium is maintained by the concerted actions in not only the epithelia of the kidney and intestine, but also bone, where turnover is a continuous process involving both resorption of existing bone and deposition of new bone, processes that are stimulated by actions of 1,25(OH) 2 D 3 and the parathyroid hormone, PTH (28, 30).The level of 1,25(OH) 2 D 3 in plasma is tightly controlled by two major cytochrome enzymes in the kidney, CYP27B1 or 1␣-hydroxylase, which converts 25(OH)D 3 to 1,25(OH) 2 D 3 , and CYP24A1, the catabolic enzyme that degrades 25(OH)D 3 and 1,25(OH) 2 D 3 to 24,25(OH) 2 D 3 and 1,24,25(OH) 3 D 3 , respectively (23). CYP24A1 is present in tissues that express VDR (3) and serves as a biomarker for VDR activation. When 1,25(OH) 2 D 3 in plasma is high, CYP24A1 becomes highly induced in the kidn...

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“…121 In addition, a similar mouse model has also been created and used to demonstrate the antitumor effects of two vitamin D analogues. 124 Sumareva et al employed the subcutaneous injection of DBA/2 mice with KLN 205 cells, a HNSCC cell line of DBA/2 mouse origin, to illustrate the effectiveness of sustained peritumoral treatment with IL-2 combined with radiation therapy. 125 Thomas et al used 4-NQO to transform oral keratinocytes derived from BALB/c mice to produce tumorigenic cell lines that have been subcutaneously injected into immunocompetent BALB/c mice.…”

Section: Subcutaneous Transplantation Modelsmentioning

confidence: 99%

Animal models for the study of squamous cell carcinoma of the upper aerodigestive tract: A historical perspective with review of their utility and limitations. Part A. Chemically‐induced de novo cancer, syngeneic animal models of HNSCC, animal models of transplanted xenogeneic human tumors

Smith

Thomas

2005

Intl Journal of Cancer

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Understanding the complex histological, genetic and molecular changes that lead to malignant transformation of squamous epithelia of the head and neck will likely guide the development of methods for improved diagnosis, monitoring and treatment of head and neck squamous cell carcinoma (HNSCC). The development and use of animal models that closely mimic the histopathology and molecular pathogenesis of HNSCC in humans would greatly expand the research possibilities and provide a means of testing potential therapeutic agents. However, many available animal models of HNSCC fall short of this objective. In order for investigators to select the appropriate model to answer scientific questions, it is important to understand the benefits and limitations of available animal models for the study of HNSCC. The purpose of this work is to give an overview of the most pertinent animal models of HNSCC, and to discuss future directions of research in this field. ' 2005 Wiley-Liss, Inc.Head and neck squamous cell carcinoma (HNSCC) involves the upper aerodigestive tract and can destroy the structure and function of organs involved in voice, speech, taste, smell and hearing, as well as vital structures necessary for survival. Approximately half of all patients with HNSCC have advanced stage disease at the time of diagnosis, with an expected 5-year survival rate between 10 and 40%.1 Despite treatments that may consist of mutilating surgery, radiotherapy and/or chemotherapy, overall long-term survival remains low due to uncontrollable persistent or recurrent disease. The survival rate of patients with locoregional and distant recurrences has highlighted the need for new approaches for diagnosis and treatment. To this end, a better understanding of the genetic, molecular and immunoregulatory processes leading to neoplastic transformation and progression of HNSCC is needed, so that novel and more effective diagnostic and therapeutic approaches can be designed.Although in vitro study systems are useful for studying the interactions between different cell populations in culture and are convenient and simple to use, they do not reproduce the complexity of HNSCC. For this reason, the development of new therapies will require clinically relevant animal models of HNSCC. Adequate animal models are necessary to test the translational potential of preventive and therapeutic agents, as well as to understand the biological mechanisms of epithelial carcinogenesis and progression. The ideal experimental animal tumor model for HNSCC must reproduce the characteristic features of the disease, including the complicated patterns of tumor-host interactions such as immune response, angiogenesis, invasion and metastasis. In the ideal model, clinical symptoms and laboratory abnormalities should be similar to the human disease and therapeutic agents should be as effective in both systems. The ideal model must also be easy to use, accessible to genetic and immunologic manipulations, reproducible and progress rapidly to allow timely investigations.Animal mod...

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Action of Low Calcemic 1 ,25-Dihydroxyvitamin D3 Analogue EB1089 in Head and Neck Squamous Cell Carcinoma

Abstract: EB1089 completely inhibited growth of AT-84 SCC cells at nanomolar concentrations, reduced tumor growth, and did not have calcemic effects. Our results support continued investigation of EB1089 as a chemopreventive/chemotherapeutic agent for head and neck SCC.

Cited by 67 publications

References 42 publications

G2/M Arrest by 1,25-Dihydroxyvitamin D3 in Ovarian Cancer Cells Mediated through the Induction of GADD45 via an Exonic Enhancer

G2/M Arrest by 1,25-Dihydroxyvitamin D3 in Ovarian Cancer Cells Mediated through the Induction of GADD45 via an Exonic Enhancer

Temporal changes in tissue 1α,25-dihydroxyvitamin D₃, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)₂D₃treatment in mice

Animal models for the study of squamous cell carcinoma of the upper aerodigestive tract: A historical perspective with review of their utility and limitations. Part A. Chemically‐induced de novo cancer, syngeneic animal models of HNSCC, animal models of transplanted xenogeneic human tumors

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Action of Low Calcemic 1 ,25-Dihydroxyvitamin D3 Analogue EB1089 in Head and Neck Squamous Cell Carcinoma

Abstract: EB1089 completely inhibited growth of AT-84 SCC cells at nanomolar concentrations, reduced tumor growth, and did not have calcemic effects. Our results support continued investigation of EB1089 as a chemopreventive/chemotherapeutic agent for head and neck SCC.

Cited by 67 publications

References 42 publications

G2/M Arrest by 1,25-Dihydroxyvitamin D3 in Ovarian Cancer Cells Mediated through the Induction of GADD45 via an Exonic Enhancer

G2/M Arrest by 1,25-Dihydroxyvitamin D3 in Ovarian Cancer Cells Mediated through the Induction of GADD45 via an Exonic Enhancer

Temporal changes in tissue 1α,25-dihydroxyvitamin D3, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)2D3treatment in mice

Animal models for the study of squamous cell carcinoma of the upper aerodigestive tract: A historical perspective with review of their utility and limitations. Part A. Chemically‐induced de novo cancer, syngeneic animal models of HNSCC, animal models of transplanted xenogeneic human tumors

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Temporal changes in tissue 1α,25-dihydroxyvitamin D₃, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)₂D₃treatment in mice