Lutein, But Not Other Carotenoids, Selectively Inhibits Breast Cancer Cell Growth Through Several Molecular Mechanisms

Abstract

IntroductionThe dietary carotenoid lutein is critical in eye and brain development and function. Its anticancer effects have been controversial, albeit understudied. We investigated effects of lutein in a wide range of receptor (+) and (−) breast cancer cell lines including difficult‐to‐treat ‘triple‐negative’ breast cancer.Materials/MethodsEight established breast cancer cell lines and primary human mammary epithelial cells (PmEC) were exposed to a concentration range of (1) carotenoids (β‐carotene, lutein, zeaxanthin, lycopene, astaxanthin); and (2) lutein + chemotherapy agents (paclitaxel, docetaxel). Cell proliferation was analyzed by MTT and EdU assays, and soft agar colony formation was assessed. Intracellular reactive oxygen species (ROS), cell cycle, and apoptosis were assayed by flow cytometry. Proteomic arrays and RT‐PCR profiling were used to evaluate changes in cellular protein phosphorylation and targeted gene expression, respectively.ResultsLutein and lutein epoxide, and to a lesser extent lycopene, but not other carotenoids, significantly inhibited breast cancer cell growth and induced cancer cell apoptosis. Lutein had little apparent effect on PmEC cell proliferation or viability. Lutein‐mediated growth inhibition is quantitatively similar to that induced by chemotherapeutic agents tested. Moreover, lutein and chemotherapy act additively‐to‐synergistically to inhibit cell growth. We determined mechanisms for growth inhibition by lutein in triple‐negative breast cancer cells include: induction of G1 cell cycle arrest; increased intracellular ROS production; mutant and wild‐type p53 phosphorylation; and down‐regulation of several anti‐apoptotic proteins, including Bcl2.ConclusionsOur findings demonstrate lutein (in concentrations attained in healthy diets) has anti‐tumor activities in human breast cancer acting via several molecular mechanisms. Lutein supplementation/fortification may be a promising nutriceutical preventive and/or adjunct therapeutic approach in a wide range of human breast cancer subtypes.Support or Funding InformationPartially funded by TTUHSC El Paso Seed Grants (LPR, XG), a Scholarly Activity & Research Program student grant (HMS), and a Summer Accelerated Biomedical Research Internship (JRS).