IPRIFLAVONE

Subject: Ipriflavone which is used to prevent osteoporosis may also prevent breast cancer metastasis to bone.

Isoflavones are natural phytoestrogens that belong to the flavonoid family of plant compounds. These plant estrogens mimic estrogens' effect on the bones, stimulating healthy bone growth in a manner similar to estrogen. They have been used in place of estrogen replacement therapy to prevent accelerated bone loss after menopause. A specific semisynthetic isoflavone called Ipriflavone appears to be particularly effective at maintaining bone mass in post menopausal women.[1 2 3]

A recent study has suggested a new use for this compound.[4] It may prove useful for women with breast cancer. If not post menopausal before being diagnosed with breast cancer, most women are menopausal after treatment. Chemotherapy is such a stress on the system that women go into menopause early. This seems to be a good thing. Women who do not go into menopause during treatment have a poorer prognosis. Some researchers have even suggested that the benefit of chemotherapy is induction of menopause and not the antitumor effect.

The problem with inducing menopause is the resultant bone loss. Without high estrogen levels the bones begin to thin rapidly. For women diagnosed with breast cancer, developing osteoporosis isn't on the top of their list of things to worry about. As one patient put it, "I should live so long...." The most common treatment used to prevent osteoporosis, hormone replacement therapy is contraindicated because it may stimulate growth of the breast cancer. This new study suggests that we can do something to prevent osteoporosis which is not only safe but which may be beneficial regarding the cancer.

In mice injected with breast cancer cells daily oral dosing with Ipriflavone significantly inhibited the development of bone metastases and the progression of already existing bone tumors. The bottom line which we always want to see, the mice taking ipriflavone lived longer.

References: 1, Agnusdei D, Bufalino L. Efficacy of ipriflavone in established osteoporosis and long-term safety. Caldif Tissue Int 1997;61 Suppl1:S23-7
2. Albanese CV et al Ipriflavone directly inhibits osteoclastic acitivity. Biochem Biophys Res Commun 1994 Mar 15;199(2):930-6
3. Anusdei D et al A double blind, placebo controlled trial of ipriflavone for prevention of postmenopausal spinal bone loss. Calcif Tissue Int 1997 Aug;61(2): 142-7
4. Iwasaki T, Mukai M, Tsujimura T, et al. Ipriflavone inhibits osteolytic bone metastasis of human breast cancer cells in a nude mouse model. Int J Cancer 2002;100:381-387

The Abstract of the Study: Int J Cancer 2002 Aug 1;100(4):381-7
Ipriflavone inhibits osteolytic bone metastasis of human breast cancer cells in a nude mouse model.

Iwasaki T, Mukai M, Tsujimura T, Tatsuta M, Nakamura H, Terada N, Akedo H.
First Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. teruteru@hyo-med.ac.jp

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-ind!

uced 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. Copyright 2002 Wiley-Liss, Inc.

PMID: 12115517 [PubMed - indexed for MEDLINE]