Antiestrogenic Glyceollins Suppress Human Breast and Ovarian Carcinoma Tumorigenesis

Abstract

Purpose: We have identified the phytoalexin compounds glyceollins I, II, and III, which exhibit marked antiestrogenic effects on estrogen receptor function and estrogen-dependent tumor growth in vivo. The purpose of this study was to investigate the interactions among the induced soy phytoalexins glyceollins I, II, and III on the growth of estrogen-dependent MCF-7 breast cancer and BG-1ovarian cancer cells implanted in ovariectomized athymic mice. Experimental Design: Four treatment groups for each cell line were used: vehicle control, 20 mg/kg/mouse/d glyceollin mixture injection, 0.72 mg estradiol (E2) implant, and E2 implant + 20 mg/kg/mouse/d glyceollin injection. Results: Treatment with glyceollin suppressed E2-stimulated tumor growth of MCF-7 cells (À53.4%) and BG-1 cells (À73.1%) in ovariectomized athymic mice. These tumor-inhibiting effects corresponded with significantly lower E2-induced progesterone receptor expression in the tumors. In contrast to tamoxifen, the glyceollins had no estrogen-agonist effects on uterine morphology and partially antagonized the uterotropic effects of estrogen. Conclusions: These findings identify glyceollins as antiestrogenic agents that may be useful in the prevention or treatment of breast and ovarian carcinoma.

Octamer 4 Small Interfering RNA Results in Cancer Stem Cell–Like Cell Apoptosis

“…In order to quantify for Oct4-positive tumor cells in established tumors, 3LL tumors were established as described above. Also, human MCF7 tumors were established as described previously (29). In brief, human MCF7 tumors were established by intradermally injecting 1 Â 10 7 tumor cells (in 50 AL of DMEM) into the back flanks of female athymic nude mice.…”

Changes in L-phenylalanine ammonia-lyase activity and isoflavone phytoalexins accumulation in soybean seedlings infected with Sclerotinia sclerotiorum

“…The biosynthetic key enzyme is reductase which synthesizes 4,2',4'-trihydroxychalcone in coaction with chalcone synthase [17]. While phytoalexins from the groups of glyceollins and coumestrol have been subject of many investigations [18][19][20][21], especially for their pharmacological effect in humans, there are few such reports for the isoflavones genistein, daidzein and glycitein when pathogen attack is involved [22][23][24]. On the other hand, accumulations of isoflavone conjugates and aglycones in soybean tissues were induced by lactofen, the active ingredient of the soybean disease resistance-inducing herbicide [25].…”

Inhibitory effect of glyceollin isolated from soybean against melanogenesis in B16 melanoma cells

“…Glyceollin has been evaluated with respect to its anti-estrogenic activity that occurs through the inhibition of estrogen receptor α and β when compared with well known phyto-estrogenic photochemicals such as genistein (20). It has also recently been recognized that glyceollin can suppress human breast and ovarian carcinoma tumorigenesis and may modulate potential estrogenic properties in the breast through anti-estrogenic effects (21). However, the biological activity of glyceollin has been poorly researched to date.…”

“…Glyceollin (mixture of glyceollin I, II, and III), which has been produced in high concentrations using several elicitors, exerts antimicrobial activity against several plant pathogens (18,19). Existing reports previously identified glyceollin as anti-estrogenic agents that may be useful in the prevention or treatment of prostate, breast and ovarian carcinoma (20,21). However, the effects of glyceollin on melanogenesis have not been evaluated to date.…”