Curcumin, a nutritional supplement with antineoplastic activity, enhances leiomyoma cell apoptosis and decreases fibronectin expression

Objective: To determine if curcumin has an antiproliferative effect on leiomyoma cells via apoptosis induction and whether curcumin impacts extracellular matrix (ECM) production by assessing the fibronectin expression in leiomyoma cells treated with curcumin. Design: Tissue culture study of immortalized human leiomyoma and patient-matched myometrial cells treated with curcumin. Setting: University hospital. Patient(s): Immortalized leiomyoma and myometrial cells from patients with symptomatic leiomyomata. Intervention(S): Tissue culture, followed by proliferation studies, RNA, and protein analysis. Main Outcome Measure(s): Cell proliferation, alteration in apoptotic signaling pathways. Result(s): Curcumin demonstrated an antiproliferative effect on leiomyoma cell tines (IC50 = 20 mu M). Importantly, no statistically significant inhibition of growth was observed when patient-matched myometrial cells were exposed to equivalent concentrations of curcumin. Curcumin stimulated caspase-3 and caspase-9 expression while inhibiting extracellular signal-regulated kinase I (ERK 1), ERK 2, and nuclear factor kappa B (NF-kappa B), suggesting regulation of leiomyocyte apoptosis. Finally, curcumin inhibited expression of fibronectin in leiomyoma cells. Conclusion(s): Our findings demonstrate that curcumin inhibited uterine leiomyoma cell proliferation via regulation of the apoptotic pathway, and inhibited production of the ECM component fibronectin. Curcumin provides a novel direction for leiomyoma. therapies. (Fertil Steril (R) 2009;91:2177-84. (C) 2009 by American Society for Reproductive Medicine.)