Dietary soy isoflavones increase metastasis to lungs in an experimental model of breast cancer with bone micro-tumors

Abstract

Bone is one of the most common sites for metastasis in breast cancer (BC). Micro-metastasis in bone marrow was detected in 30% of patients with stage I, II, or III BC at primary surgery and is a strong indicator of poor prognosis. The role dietary soy isoflavones play in BC with bone micro-metastasis is unclear. In this study, we examined the effects of genistein, daidzein, (−)-equol or a mixture of soy isoflavones on BC with bone micro-metastasis using an experimental model of murine mammary cancer 4T1 cells engineered with luciferase. A small number (1,000) of 4T1 cells were injected into the tibia of female Balb/c mice to establish micro-tumors in bone. Soy isoflavones were supplemented in the AIN-93G diet at 750 mg/kg and were provided to mice from 3 weeks before to 3 weeks after cell injection. Bioluminescent imaging was conducted on day 2 (D2), D6, D8, D16 and D20 post cell injection and the results indicated dietary soy isoflavones enhanced the growth of bone micro-tumors on D8. Furthermore, dietary soy isoflavones stimulated metastatic tumor formation in lungs and increased Ki-67 protein expression in these metastasized tumors. In vitro, soy isoflavones (< 10 µM) had limited effects on the growth, motility or invasion of 4T1 cells. Thus, the in vivo stimulatory effect could be likely due to systemic effects between the host, 4T1 tumors and soy isoflavones. In conclusion, soy isoflavones stimulate BC with bone micro-metastasis in mice and further investigations are needed regarding their consumption by BC survivors.

Pro-oxidant activity of polyphenols and its implication on cancer chemoprevention and chemotherapy

“…Furthermore, the co-treatment of HeLa cells with 7and MRP2)[94]. Nevertheless, the effect of isoflavones on cancer remains controversial, as a recent study has shown that dietary soy isoflavones, including genistein, daidzein and (-)-equol, increased the formation of metastatic tumor nodules in lungs using an in vivo murine model of breast cancer with bone breast 4T1 cells micro-metastases[95].…”

Phytoestrogens: The current state of research emphasizing breast pathophysiology

“…There is some evidence that shows soy isoflavones such as daidzein can enhance cancer characteristics in mouse mammary tumor cell lines (Koo et al, ; Yang et al, ). In addition, in vivo studies also point to the possibility that soy isolfavones might interfere with the therapeutic effect of tamoxifen (Du et al, ).…”

Fitoösztrogének a menopauza terápiájában

“…Genisztein esetében 28%, daidzein esetében 35,9%, equolos csoportnál 28,6%, több izoflavonoiddal együtt kezelt egyedeknél ez az érték pedig 34,3% volt. A kísér-let tehát a fitoösztrogének metasztázisképzést fokozó hatását bizonyította, ennek alapján is felvetődik a gondolat, hogy rákban szenvedőknél kockázattal járhat fogyasztásuk [37].…”