ArticleCancer prevention research (Philadelphia, Pa.)2008
Gemini vitamin D analogues inhibit estrogen receptor-positive and estrogen receptor-negative mammary tumorigenesis without hypercalcemic toxicity.
Article in Cancer prevention research (Philadelphia, Pa.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Vitamin D intake, blood 25(OH)D levels, and breast cancer risk or mortality: a meta-analysis.British journal of cancer · 2014Pooled it
- Therapeutic implications of vitamin D in leukemia: mechanistic and clinical perspectives.Medical oncology (Northwood, London, England) · 2025Review
- Vitamin D in Cancer Prevention and Treatment: A Review of Epidemiological, Preclinical, and Cellular Studies.Cancers · 2024Review
- Effects of 1α,25-dihydroxyvitamin DBiochemistry and biophysics reports · 2022Article
- Vitamin D, Th17 Lymphocytes, and Breast Cancer.Cancers · 2022Review
- Combinations of Calcitriol with Anticancer Treatments for Breast Cancer: An Update.International journal of molecular sciences · 2021Review
- Single-cell analyses unravel cell type-specific responses to a vitamin D analog in prostatic precancerous lesions.Science advances · 2021Article
- Structural analysis and biological activities of BXL0124, a gemini analog of vitamin D.The Journal of steroid biochemistry and molecular biology · 2017Article
- Influence of vitamin D signaling on hormone receptor status and HER2 expression in breast cancer.Journal of cancer research and clinical oncology · 2017Review
- Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.Physiological reviews · 2016Review
- HES1-mediated inhibition of Notch1 signaling by a Gemini vitamin D analog leads to decreased CD44(+)/CD24(-/low) tumor-initiating subpopulation in basal-like breast cancer.The Journal of steroid biochemistry and molecular biology · 2015Article
- Inhibition of the transition of ductal carcinoma in situ to invasive ductal carcinoma by a Gemini vitamin D analog.Cancer prevention research (Philadelphia, Pa.) · 2014Article
- The future of vitamin D analogs.Frontiers in physiology · 2014Review
- Oral administration of a gemini vitamin D analog, a synthetic triterpenoid and the combination prevents mammary tumorigenesis driven by ErbB2 overexpression.Cancer prevention research (Philadelphia, Pa.) · 2013Article
- Article
- Chaperone properties of pdia3 participate in rapid membrane actions of 1α,25-dihydroxyvitamin d3.Molecular endocrinology (Baltimore, Md.) · 2013Article
- Equivalent anticancer activities of dietary vitamin D and calcitriol in an animal model of breast cancer: importance of mammary CYP27B1 for treatment and prevention.The Journal of steroid biochemistry and molecular biology · 2013Review
- Hydroxylation of CYP11A1-derived products of vitamin D3 metabolism by human and mouse CYP27B1.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Vitamin d: are we ready to supplement for breast cancer prevention and treatment?ISRN oncology · 2013Article
- Targeting CD44-STAT3 signaling by Gemini vitamin D analog leads to inhibition of invasion in basal-like breast cancer.PloS one · 2013Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Numerous preclinical, epidemiologic, and clinical studies have suggested the benefits of vitamin D and its analogues for the prevention and treatment of cancer. However, the hypercalcemic effects have limited the use of 1alpha,25(OH)(2)D(3), the hormonally active form of vitamin D. To identify vitamin D analogues with better efficacy and low toxicity, we have tested >60 novel Gemini vitamin D analogues with a unique structure of two side chains for growth inhibition of breast cancer cells. Our initial studies found that some Gemini analogues are 5-15 times more active than 1alpha,25(OH)(2)D(3) in growth inhibition assay. In vivo experiments were designed to study the inhibitory effect of selected Gemini vitamin D analogues against mammary carcinogenesis by using (a) an N-methyl-N-nitrosourea-induced estrogen receptor (ER)-positive mammary tumor model and (b) an MCF10DCIS.com xenograft model of ER-negative mammary tumors. Among vitamin D analogues we tested, Gemini 0072 [1alpha,25-dihydroxy-20S-21(3-trideuteromethyl-3-hydroxy-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluoro-19-nor-cholecalciferol] and Gemini 0097 [1alpha,25-dihydroxy-20R-21(3-trideuteromethyl-3-hydroxy-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluoro-19-nor-cholecalciferol] administration inhibited by 60% the NMU-induced mammary tumor burden compared with the NMU-treated control group, but these compounds were devoid of hypercalcemia toxicity. In an ER-negative xenograft model, Gemini 0097 significantly suppressed tumor growth without hypercalcemia toxicity. We found that the inhibitory effect of Gemini 0097 was associated with an increased level of cyclin-dependent kinase inhibitor p21 and the insulin-like growth factor binding protein 3 in both ER-positive and ER-negative mammary tumors. Our results suggest that Gemini vitamin D analogues may be potent agents for the prevention and treatment of both ER-positive and ER-negative breast cancer without hypercalcemia toxicity.
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