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ABSTRACT: Ipriflavone inhibits osteolytic bone metastasis of human
breast cancer cells in a nude mouse model
Osteolytic bone metastasis is a frequent problem in the treatment of
cancer.
Ipriflavone, a synthetic isoflavone that inhibits osteoclastic
bone resorption, has been used for the treatment of osteoporosis
in some countries.
Some other isoflavones also exhibit an antitumor
effect in vitro and in vivo.
Here, we studied the effects of
ipriflavone on osteolytic bone metastasis of MDA-231 human breast
cancer cells injected intracardially into athymic nude mice (ICR-nu/nu).
Daily oral administration of ipriflavone at 12 mg/mouse significantly
inhibited the development of new osteolytic bone metastases (p
< 0.05) and the progression of established osteolytic lesions
(p = 0.01), prolonging the life of tumor-bearing mice (p = 0.01
vs. control).
In addition, ipriflavone reduced the number of
osteoclasts at the bone-cancer interface with no severe adverse
effects on the host. In vitro, ipriflavone inhibited the proliferation
and DNA synthesis of MDA-231 cells and blocked the ligand-induced
phosphorylation of Tyr845 of the EGFR.
Ipriflavone did not promote
apoptosis of MDA-231 cells. Our results show that ipriflavone
not only directly inhibits the growth of cancer cells but also
reduces osteoclasts to prevent the soft tissue tumor burden and
osteolytic bone metastases.
These findings raise the possibility
that ipriflavone may be of use as a therapeutic agent against
osteolytic bone metastasis.
[07/09/2002; International Journal of Cancer]
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