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Vitamin
D3 is a potent inhibitor of tumor cell-induced angiogenesis
Majewski
S, Skopinska M, Marczak M, Szmurlo A, Bollag W, Jablonska S
Department
of Dermatology, Warsaw School of Medicine, Poland
Vitamin
D3 derivative 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) exerts various biological
effects in cells that possess vitamin D3 receptor (VDR), including enhancement
of cell differentiation and inhibition of cell proliferation.
These activities of 1,25(OH)2D3 might be responsible for its anti-neoplastic
effects, as shown in various experimental systems.
The aim of this study was to compare the anti-angiogenic activity of
1,25(OH)2D3, retinoids, and interleukin-12 (IL-12) in an experimental tumor
cell-induced angiogenesis assay in mice.
Tumor cell-induced angiogenesis assay was performed in x-ray immunosuppressed
BALB/c mice by intradermal injections of human tumor cell lines of different
origin.
The injections resulted within 3 d in a local formation of new blood vessels,
and the intensity of angiogenesis correlated with the number of injected cells.
Systemic treatment of the mouse recipients with 1,25(OH)2D3 significantly
decreased angiogenesis, comparable to the effect of retinoids (all-trans
retinoic acid [RA], 9-cis RA and 13-cis RA) and of IL-12.
In vitro preincubation of the cells with all compounds (except IL-12) led to the
inhibition of their angiogenic capability in vivo. Moreover, combination of
1,25(OH)2D3 and retinoids resulted in a synergistic inhibition of angiogenesis.
The results strongly suggest that anti-angiogenic compounds with relatively low
toxicity (e.g., 1,25(OH)2D3, retinoids, and IL-12) and their combinations could
be beneficial in the treatment of some angiogenesis-associated malignancies.
PMID:
9627702 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9627702&dopt=Abstract
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