1 alpha,25-Dihydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3 prolong survival time of mice inoculated with myeloid leukemia cells.

Honma, Yoshio; Hozumi, Motoo; Abe, Etsuko; Konno, Kunio; Fukushima, Masafumi; Hata, Shun-ichi; Nishii, Yasuho; DeLuca, Hector F.; Suda, Toshio

doi:10.1073/pnas.80.1.201

Cited by 230 publications

(91 citation statements)

References 35 publications

(40 reference statements)

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“…To examine the effects of hypergravity on vitamin D-regulated gene expression, we treated mice with 1␣(OH)D 3 via intraperitoneal injection. 1␣(OH)D 3 is rapidly converted to 1,25(OH) 2 D 3 after injection and is more effective than 1,25(OH) 2 D 3 in prolonging survival time in a mouse model of leukemia (11). As reported previously (13,27), 1␣(OH)D 3 induced mRNA expression of VDR target genes, Cyp24a1, calbindin D9k, Trpv5, and Trpv6, in the kidney of ICR mice (Fig.…”

Section: Effects Of Hypergravity On Gene Expression In Icr Micesupporting

confidence: 53%

Hypergravity modulates vitamin D receptor target gene mRNA expression in mice

Ishizawa

Iwasaki²,

Kato³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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The possibility of pathological calcium metabolism is a critical health concern introduced by long-term space travel. Because vitamin D plays an important role in calcium homeostasis, we evaluated the effects of hypergravity on the expression of genes involved in vitamin D and calcium metabolism in ICR mice. When exposed to 2G hypergravity for 2 days, the mRNA expression of renal 25-hydroxyvitamin D 24-hydroxylase (Cyp24a1) was increased and that of 25-hydroxyvitamin D 1␣-hydroxylase (Cyp27b1) was decreased. Although hypergravity decreased food intake and increased the expression of starvation-induced genes, the changes in Cyp24a1 and Cyp27b1 expression were not due to starvation, suggesting that hypergravity affects these genes directly. Hypergravity decreased plasma 1␣,25-dihydroxyvitamin D3 levels in ICR mice, suggesting a consequence of decreased Cyp27b1 and increased Cyp24a1 expression. Although 1␣-hydroxyvitamin D3 [1␣(OH)D3] treatment induced the expression of vitamin D receptor (VDR) target genes in the kidney of 2G-exposed ICR mice to similar levels as controls, 1␣(OH)D3 increased the intestinal expression of Cyp24a1 in ICR mice. Hypergravity-dependent changes of Cyp24a1 and Cyp27b1 expression were diminished in mice exposed to hypergravity for 14 days, which may represent an adaptation to hypergravity stress. Hypergravity exposure also increased Cyp24a1 expression in the kidney of C57BL/6J mice. We examined the effects of hypergravity on VDRnull mice and found that renal Cyp27b1 expression in VDR-null mice was decreased by hypergravity while renal Cyp24a1 expression was not detected in VDR-null mice. Thus hypergravity modifies the expression of genes involved in vitamin D metabolism. 12), and vitamin D 2 is less effective than vitamin D 3 in maintaining serum 25(OH)D levels (1). Vitamin D deficiency, mainly caused by inadequate sun exposure, results in rickets and osteomalacia, and is also associated with increased risk of cancer, autoimmune disease, infection, and cardiovascular disease (10). 1,25(OH) 2 D 3 exhibits physiological and pharmacological effects by binding to the vitamin D receptor (VDR; NR1I1), a transcription factor of the nuclear receptor superfamily, which is highly expressed in the target organs of calcium homeostasis, such as the intestine, bone, kidney, and parathyroid glands (6, 21). VDR regulates the expression of many target genes, including 25-hydroxyvitamin D 24-hydroxylase (CYP24A1), calbindin D9k, and transient receptor potential vanilloid type 6 (TRPV6).Bone mineral loss is one of the critical health concerns raised by the prospect of long-term space travel (19,29). Space flight induces uncoupled bone remodeling, including increased bone resorption and urinary calcium excretion and decreased calcium absorption. Vitamin D deficiency due to the absence of ultraviolet light and decreased dietary intake of vitamin D during space flight has been considered to be one reason for dysregulated bone and calcium metabolism (30). Supplemental vitamin D and calcium intake increase blood...

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Section: Effects Of Hypergravity On Gene Expression In Icr Micesupporting

confidence: 53%

Hypergravity modulates vitamin D receptor target gene mRNA expression in mice

Ishizawa

Iwasaki²,

Kato³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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“…1,25-Dihydroxyvitamin D3 (calcitriol, 1,25D3) is well known to induce differentiation of leukaemic cells (Abe et al, 1981;Honma et al, 1983). This differentiation is linked to exit from the cell cycle at the restriction (R) point in late GI stage, resulting in growth inhi-bition, which suggests a new strategy for cancer therapy (Pardee, 1974).…”

mentioning

confidence: 99%

Vitamin D analogues up-regulate p21 and p27 during growth inhibition of pancreatic cancer cell lines

Kawa

Nikaido²,

Aoki³

et al. 1997

Br J Cancer

111

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Summary To obtain information regarding the growth-inhibitory effect of 1,25-dihydroxyvitamin D3 and its non-calcaemic analogue 22-oxa-1,25-dihydroxyvitamin D3 on pancreatic cancer cell lines, differences in the effects of Gl-phase cell cycle-regulating factors were studied in vitamin D-responsive and non-responsive cell lines. Levels of expression of cyclins (D1, E and A), cyclin-dependent kinases (2 and 4) and cyclin-dependent kinase inhibitors (p21 and p27) were analysed by Western blotting after treatment with these compounds. In the responsive cells (BxPC-3, Hs 700T and SUP-1), our observations were: (1) marked up-regulation of p21 and p27 after 24 h treatment with 10-7 mol 1-' 1,25-dihydroxyvitamin D3 and 22-oxa-1,25-dihydroxyvitamin D3; and (2) marked down-regulation of cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors after 7 days' treatment. In non-responsive cells , no such changes were observed.In conclusion, vitamin D analogues up-regulate p21 and p27 as an early event, which in turn could block the G,/S transition and induce growth inhibition in responsive cells.

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“…1,25-dihydroxyvitamin D 3 , calcitriol, an active form of vitamin D 3 , has been reported to induce differentiation and inhibit the proliferation of various types of cancer cells in addition to its well-known biological activities in enhancing intestinal calcium transport and bone and mineral mobilization [2][3][4][5]. However, clinical application of this compound is limited because of its hypercalcemia-inducing activity.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of 22-oxa-1,25-dihydroxyvitamin D3, maxacalcitol, on the proliferation of pancreatic cancer cell lines

Kawa

Yoshizawa

Nikaido

et al. 2005

The Journal of Steroid Biochemistry and Molecular Biology

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Effective chemotherapy for pancreatic cancer is urgently needed. The aim of this study was to compare the anti-proliferative activity on pancreatic cancer cell lines of the vitamin D 3 analog, 22-oxa-1,25-dihydroxyvitamin D 3 , maxacalcitol, with that of 1,25-dihydroxyvitamin D 3, calcitriol, with analysis of vitamin D receptor status and the G 1 -phase cell cycle-regulating factors.Antiproliferative effects of both agents were compared using the 3-(4,5-dimethyl thiazol-2-yl)--2,5-diphenyltetrazolium bromide method and by measuring the tumor size of xenografts inoculated into athymic mice. Scatchard analysis of vitamin D receptor contents, and mutational analysis of receptor complementary DNA were performed. Levels of expression of cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors, p21 and p27, were analysed by western blotting.In vitro, maxacalcitol and calcitriol markedly inhibited the proliferation and caused a G 1 phase cell cycle arrest with the appearance of numerous domes. In vivo, maxacalcitol inhibited the growth of BxPC-3 xenografts more significantly than calcitriol, without inducing hypercalcemia. Responsive cells had abundant functional vitamin D receptors. However, Hs 766T, showing no response to either agent, had the second highest receptor contents with no abnormalities in its primary structure deduced by receptor complementary DNA. In the responsive cells, p21 and p27 were markedly up-regulated after 24 hours of treatment with both agents. In non-responsive cells, no such changes were observed. In conclusion, maxacalcitol and calcitriol up-regulate p21 and p27 as an early event, which in turn could block the G 1 /S transition and induce growth inhibition in responsive cells, and maxacalcitol may provide a more useful tool for the chemotherapy of pancreatic cancer than calcitriol because of its low toxicity.

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1 alpha,25-Dihydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3 prolong survival time of mice inoculated with myeloid leukemia cells.

Cited by 230 publications

References 35 publications

Hypergravity modulates vitamin D receptor target gene mRNA expression in mice

Hypergravity modulates vitamin D receptor target gene mRNA expression in mice

Vitamin D analogues up-regulate p21 and p27 during growth inhibition of pancreatic cancer cell lines

Inhibitory effect of 22-oxa-1,25-dihydroxyvitamin D3, maxacalcitol, on the proliferation of pancreatic cancer cell lines

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