Lutein inhibits breast cancer cell growth by suppressing antioxidant and cell survival signals and induces apoptosis.

Reduced risk of breast cancer upon intake of lutein‐rich food supplements creates
an interest to investigate the molecular mechanism underlying the growth inhibitory
potential of lutein in MCF‐7 and MDA‐MB‐231 cells. Lutein purified from Spinacia
oleracea was identified by high‐performance liquid chromatography and liquid
chromatography–mass spectrometry. The cell viability was measured by water‐
soluble tetrazolium‐1 assay. The intracellular reactive oxygen species level was
examined by 2′,7′‐dichlorofluorescein assay. The protein expression of the markers
of antioxidant defense, cell survival, and apoptosis was analyzed by western blot
analysis. The induction of apoptosis by lutein was measured by 4′,6‐diamidino‐2‐
phenylindole staining and caspase‐3 activity assay. The purified lutein inhibited the
viability of MCF‐7 and MDA‐MB‐231 cells. The growth inhibitory effect of lutein
was associated with suppressed protein expression of superoxide dismutase‐2 and
heme oxygenase‐1, and its transcription factor nuclear factor erythroid 2‐related
factor‐2. Lutein treatment subsequently blocked the expression of intracellular cell
survival proteins, phosphorylated protein kinase B, phosphorylated extracellular‐
regulated kinase 1/2, and nuclear factor‐kB. Suppression of antioxidant defense and
cell survival markers by lutein was further linked to apoptosis induction with
elevated caspase‐3 activity and downregulated expression of Bcl‐2 and poly‐ADP
ribose polymerase. Our results emphasize a significant role of lutein as an effective
inhibitor of human breast cancer cell growth that activates cell death partly through
the modulation of antioxidant defense response‐linked cell survival signaling
markers.