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 Tyr(845) 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.