Inhibition of prostate cancer-meditated osteoblastic bone lesions by the low-calcemic analog 1α-hydroxymethyl-16-ene-26,27-bishomo-25-hydroxy vitamin D3

Peleg, Sara; Khan, Farhana; Navone, Nora M.; Cody, Dianna D.; Johnson, Evan M.; Pelt, Carolyn S. Van; Posner, Gary H.

doi:10.1016/j.jsbmb.2005.06.015

Cited by 11 publications

(4 citation statements)

References 25 publications

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“…As in C4-2 cells, 1,25(OH) 2 D 3 and EB1089 decrease MDA-MB-231 cell proliferation but have no effect on apoptosis (32). Another low-hypercalcemic 1,25(OH) 2 D 3 analog, JK-1626-2, also decreased the incidence of bone lesions induced by MDA-PCa-2b cells injected into the tibia (50). However, in that study, treatment with the analogue only prevented the development of bone lesions; tumor cells were still present in the diaphysis of ~70% of treated mice (50).…”

Section: Discussionmentioning

confidence: 98%

“…Another low-hypercalcemic 1,25(OH) 2 D 3 analog, JK-1626-2, also decreased the incidence of bone lesions induced by MDA-PCa-2b cells injected into the tibia (50). However, in that study, treatment with the analogue only prevented the development of bone lesions; tumor cells were still present in the diaphysis of ~70% of treated mice (50). Differences in the protective effects of these analogs may be attributed to properties of the analogs themselves, different cell lines used in the two studies, and/or the routes of administration used (intracardiac vs. intratibial).…”

Section: Discussionmentioning

confidence: 98%

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EB1089 inhibits the parathyroid hormone–related protein–enhanced bone metastasis and xenograft growth of human prostate cancer cells

Bhatia

Saini

Shen

et al. 2009

Molecular Cancer Therapeutics

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Parathyroid hormone-related protein (PTHrP) plays a major role in prostate carcinoma progression and bone metastasis. Once prostate cancers become androgen-independent, treatment options become limited. Vitamin D analogues represent a potentially valuable class of agents in this clinical context. Using the prostate cancer cell line C4-2 as a model, we studied the effects of PTHrP and the noncalcemic vitamin D analogue EB1089 on markers of prostate cancer cell progression in vitro and in vivo. C4-2 is a second-generation androgen-independent LNCaP subline that metastasizes to the lymph nodes and bone when injected into nude mice and produces mixed lytic/blastic lesions, mimicking the in vivo situation. We report that PTHrP increases cell migration and invasion, and that a pathway via which EB1089 inhibits these processes is through down-regulation of PTHrP expression. PTHrP also increases anchorage-independent cell growth in vitro and xenograft growth in vivo; EB1089 reverses these effects. The in vivo PTHrP effects are accompanied by increased tumor cell proliferation and survival. Treatment with EB1089 reverses the proliferative but not the antiapoptotic effects of PTHrP. PTHrP also increases intratumor vessel density and vascular endothelial growth factor expression; EB1089 reverses these effects. Intracardially injected C4-2 cells produce predominantly osteoblastic lesions; PTHrP overexpression decreases the latency, increases the severity and alters the bone lesion profile to predominantly osteolytic. EB1089 largely reverses these PTHrP effects. A direct correlation between PTHrP immunoreactivity and increasing tumor grade is observed in human prostate cancer specimens. Thus, decreasing PTHrP production by treatment with vitamin D analogues may prove therapeutically beneficial for prostate cancer.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

EB1089 inhibits the parathyroid hormone–related protein–enhanced bone metastasis and xenograft growth of human prostate cancer cells

Bhatia

Saini

Shen

et al. 2009

Molecular Cancer Therapeutics

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“…148 Numerous studies have examined the ability of dietary or pharmacologic addition of vitamin D compounds to either prevent tumor formation or inhibit the growth of xenograft tumors. 82,[149][150][151][152][153][154][155][156][157][158][159] One area of investigation is the impact of experimental dietary variations and their impact on tumor predisposition. Long-term studies of mice fed with a Western-style diet (eg, high fat and phosphate and low vitamin D and calcium content) have been exploited to examine the impact of vitamin D on colon cancer proliferation.…”

Section: In Vivo Vitamin D Receptor Anticancer Actionsmentioning

confidence: 99%

Vitamin D Receptor Signaling and Cancer

Campbell

Trump

2017

Endocrinology and Metabolism Clinics of North America

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The primary biological action of the secosteroid hormone vitamin D (1,25(OH) 2 D 3 ) is to bind to the vitamin D receptor (NR1I1/VDR) and to regulate serum calcium levels. As a downstream consequence, the actions of the receptor control bone formation and maintenance. The first clinical manifestation of insufficient VDR endocrine signaling, rickets, was discovered by Daniel Whistler in the Netherlands in the 17th century; 300 years later, the VDR gene was cloned by Bert O'Malley and coworkers. 1 Between these dates, research into vitamin D was at the forefront of areas of public health, chemistry and biochemistry including the light catalyzed synthesis of vitamin D 3 by Adolf Windaus. For this work, he received the Nobel Prize in Chemistry (1928). Work in the 1960s and 1970s led to analyses of vitamin D endocrine metabolism and led to remarkable strides describing biochemical synthesis of 1,25(OH) 2 D 3 and the diverse biology in which VDR participates.The precursor of 1,25(OH) 2 D 3 , cholecalciferol or vitamin D 3 , is produced in the skin and converted in the liver to 25-hydroxyvitamin D 3 , (25(OH)D 3 ); circulating levels of 25(OH)D 3 serve as a useful index of vitamin D total body stores. A further hydroxylation occurs in the principally in the kidney at the carbon 1 position by 25-hydroxyvitamin D-1α-hydroxylase (encoded by CYP27B1) to produce the biologically active hormone, 1,25(OH) 2 D 3 . A second mitochondrial cytochrome P450 enzyme, the 24-hydroxylase (encoded by CYP24A1), can use both 25(OH)D and 1,25(OH) 2 D 3 as substrates, and is the first step in the inactivation pathway for these metabolites. Because of the direct role 1,25(OH) 2 D 3 plays in control of serum calcium levels, elevated levels of 1,25(OH) 2 D 3 block its synthesis and induce inactivation and accelerate catabolism 2 via induction of CYP24A1, in a classical negative feedback loop.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). The first report that VDR actions could control cancer cell growth were discovered partly through serendipity, and partly through logical extension of other studies. Reports in the 1970s identified purified cell fractions that bound 1,25(OH) 2 D 3 with high affinity, 14 and encouraged investigators to begin to consider what were the molecular actions of the VDR in the classic tissues involved in calcium homeostasis, for example, skin, bone, intestine, and kidney. 15 In 1981, Kay Colston and coworkers 16 were first to demonstrate that 1α,25(OH) 2 D 3 at nanomolar concentrations inhibited human melanoma cell proliferation in vitro. That the workers used a cancer cell model was serendipitous; cancer cell models are more readily available to study in cell culture experiments than nonmalignant counterparts, and in this case 16 the cells chosen were available in an adjacent laboratory. Campbell and Trump In parallel, it was also known that retinoids, which are also small lipophilic molecules that target NRs, could drive cell differentiation, for exa...

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“…[43]), the A ring (e.g. [44,45]) or CD ring structure [46]. In addition, combination therapy of Vitamin D analogs with other classical chemotherapeutic agents (e.g.…”

Section: Intervention Trials With Vitamin 125(oh) 2 D or Vitamin D mentioning

confidence: 99%

Vitamin D and cancer

Bouillon¹,

Eelen²,

Verlinden³

et al. 2006

The Journal of Steroid Biochemistry and Molecular Biology

204

135

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Inhibition of prostate cancer-meditated osteoblastic bone lesions by the low-calcemic analog 1α-hydroxymethyl-16-ene-26,27-bishomo-25-hydroxy vitamin D3

Cited by 11 publications

References 25 publications

EB1089 inhibits the parathyroid hormone–related protein–enhanced bone metastasis and xenograft growth of human prostate cancer cells

EB1089 inhibits the parathyroid hormone–related protein–enhanced bone metastasis and xenograft growth of human prostate cancer cells

Vitamin D Receptor Signaling and Cancer

Vitamin D and cancer

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