Inhibition of Human Breast Cancer Cells by Citrus Limonoids

Citrus limonoids are a class of chemically related compounds present in lemon, lime, orange and grapefruit. We have shown that nomilin and a limonoid glucoside mixture are potent inhibitors of prolifertation of estrogen receptor-negative (ER-) and -positive (ER+) human breast cancer cells in culture. In the present experiments, we tested deacetylnomilin, deoxylimonin, ichangin, isoobacunoic acid, limonol, limonin carboxymethoxime, methyl deoxylimonate, methylnomilinate methyl deacetylnomilinate, methyl isolimonate, nomilin glucoside, nomilinic acid glucoside, 7a-obacunol, obacunone and obacunone glucoside for their ability to inhibit the proliferation of MDA-MB-435 ER- and MCF-7 ER+ human breast cancer cells. In ER- cells, limonin methoxime and deacetylnomilin were the most effective inhibitors having IC50s of 0.02 and 0.07 ug/mL respectively. In ER+ cells, deacetylnomilin, obacunone and methyl nomilinate were the most effective inhibitors of proliferation having IC50s of 0.005, 0.009 and 0.01 ug/mL respectively. Maximum tolerated dose studies were conducted in nude mice for limonin and the glucoside