Toward Therapeutic Intervention of Cancer by Vitamin D Compounds

Campbell, Moray J.; Koeffler, H. Phillip

doi:10.1093/jnci/89.3.182

Cited by 54 publications

(21 citation statements)

References 38 publications

(37 reference statements)

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“…The 1,25(OH) 2 D 3 and many of its synthetic analogs inhibit the growth of malignant cells (16). However, translation of the cellular results into in vivo studies has been problematic because of acute toxicity of the hormone and some of its analogs.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Proliferation and Induction of Apoptosis by 25-Hydroxyvitamin D3-3β-(2)-Bromoacetate, a Nontoxic and Vitamin D Receptor-Alkylating Analog of 25-Hydroxyvitamin D3 in Prostate Cancer Cells

Swamy

Chen

Peleg

et al. 2004

Clinical Cancer Research

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Section: Resultsmentioning

confidence: 99%

Inhibition of Proliferation and Induction of Apoptosis by 25-Hydroxyvitamin D3-3β-(2)-Bromoacetate, a Nontoxic and Vitamin D Receptor-Alkylating Analog of 25-Hydroxyvitamin D3 in Prostate Cancer Cells

Swamy

Chen

Peleg

et al. 2004

Clinical Cancer Research

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“…1,25(OH) 2 D 3 induces differentiation of normal cells including those from hematopoietic, digestive and integumentary systems (Reichel et al 1989). 1,25(OH) 2 D 3 can also inhibit proliferation and induced differentiation of various cancer cells, such as those from breast, ovary, skin, colon, brain and prostate tissue as well as leukemia cells (Campbell & Koeffler 1997, Colston 1997, Gross et al 1997, Van Leeuwen & Pols 1997. Previous studies have shown that both a genomic and non-genomic pathway are involved in these regulatory actions (Norman 1997).…”

Section: Introductionmentioning

confidence: 99%

Effects of long-term administration of vitamin D3 analogs to mice

Smith

Frankenburg²,

Goldstein³

et al. 2000

Journal of Endocrinology

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This study explores the effects of chronic administration of vitamin D 3 compounds on several biological functions in mice. Knowledge of long-term tolerability of vitamin D 3 analogs may be of interest in view of their potential clinical utility in the management of various pathologies such as malignancies, immunological disorders and bone diseases. Four unique vitamin D 3 analogs (code names, compounds V, EO, LH and LA) and 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) were administered i.p. for 55 weeks to Balb/c mice. Each analog had previously been shown to have potent in vitro activities. After 55 weeks of administration, the mice had a profound decrease in their serum levels of interleukin-2 (IL-2). Likewise, several analogs depressed serum immunoglobulin G concentrations (compounds LH and LA), but levels of blood lymphocytes and splenic lymphocyte subsets (CD4, CD8 and CD19) were not remarkably depressed. The percent of committed myeloid hematopoietic stem cells was 4-to 5-fold elevated in the bone marrow of the mice that received analogs LH and V; nevertheless, their peripheral blood white and red cell counts and platelets were not significantly different in any of the groups. The mice that received 1,25(OH) 2 D 3 had a decrease in bone quantity and quality with a decrease in cross-sectional area and cortical thickness, and a 50% reduction in both stiffness and failure load compared with the control group. In contrast, the cohort that received a fluorinated analog (compound EO) developed bones with significantly larger cross-sectional area and cortical thickness as well as stronger mechanical properties compared with the control group. At the conclusion of the study, body weights were significantly decreased in all experimental mice. Their blood chemistries were normal. Extensive gross and microscopic autopsy analyses of the mice at the conclusion of the study were normal, including those of their kidneys. In conclusion, the vitamin D 3 analogs were fairly well tolerated. They did suppress immunity as measured by serum IL-2 and may provide a means to depress the immune response after organ transplantation and for autoimmune diseases. Use of these analogs prevented the detrimental effects of vitamin D 3 administration on mechanical and geometric properties of bone, while one analog (compound EO) actually enhanced bone properties. These results suggest that long-term clinical trials with the analogs are feasible.

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“…Moreover, this molecule showed synergism with dexamethasone and several chemotherapeutic agents. Its antineoplastic activity seems to be dose dependent [72]. Beer et al [31] evaluated combination therapy with vitamin D (0.5 µg/kg/week) + weekly docetaxel (36 mg/m 2 ) and obtained a PSA response of 81% with good tolerance.…”

Section: Biomolecular Therapiesmentioning

confidence: 99%

Present Status and Perspectives in the Treatment of Hormone-Refractory Prostate Cancer

Silvestris¹,

Leone²,

Numico

et al. 2005

Oncology

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The cornerstone in the treatment of de novo or recurrent metastatic prostate cancer is androgen deprivation. Unfortunately, nearly all patients will develop androgen-independent (‘hormone-refractory’) disease with progressive clinical deterioration and ultimately death. Chemotherapy has been shown to palliate symptoms of hormone-refractory disease but not to improve survival. Recently, two large phase III trials have demonstrated an overall survival advantage for patients treated with docetaxel-based regimens as compared to the best standard of care. Indeed, investigations into the pathophysiology of this malignancy, novel biological agents, skeletal protectants and radiopharmaceuticals are expanding the clinician’s armamentarium and improving the patient’s outcome.

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Toward Therapeutic Intervention of Cancer by Vitamin D Compounds

Cited by 54 publications

References 38 publications

Inhibition of Proliferation and Induction of Apoptosis by 25-Hydroxyvitamin D3-3β-(2)-Bromoacetate, a Nontoxic and Vitamin D Receptor-Alkylating Analog of 25-Hydroxyvitamin D3 in Prostate Cancer Cells

Inhibition of Proliferation and Induction of Apoptosis by 25-Hydroxyvitamin D3-3β-(2)-Bromoacetate, a Nontoxic and Vitamin D Receptor-Alkylating Analog of 25-Hydroxyvitamin D3 in Prostate Cancer Cells

Effects of long-term administration of vitamin D3 analogs to mice

Present Status and Perspectives in the Treatment of Hormone-Refractory Prostate Cancer

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