Inhibition of Mammary Cancer by Citrus Limonoids

摘要

Limonoids have been shown to inhibit breast cancer cellular proliferation in estrogen receptor negative (ER-) and positive (ER+) cells. Nude mice were given limonoids in both treatment and adjuvant-based models to observe their effects on the proliferation of established and resected tumours respectively. It was found that limonoids, particularly limonin, slowed tumour growth and was able to prevent or delay the regrowth of resected tumours in these models. Additionally, limonoids were detected in mammary tissue samples of mice from the treatment model experiment, indicating that these compounds are bioavailable and were responsible for the observed results. To elucidate the mechanisms by which limonoids inhibit cellular proliferation, their influence on the cell cycle and abilities to induce apoptosis were investigated. MDA-MB-435 cells were found to accumulate in the G2M phase of the cell cycle after 72 hours of incubation with limonoids at their IC50 values. However, these compounds were not found to induce apoptosis in ER(-) cells when incubated for 48 hours at levels Known to be cytostatic. Therefore, the mechanism by which citrus limonoids inhibit cellular proliferation in vitro and in vivo is via modulation of the cell cycle.