Abstract
Increasing evidence suggests that dietary carotenoids may reduce the risk of breast cancer. However, anti-breast cancer effects of carotenoids have been controversial, albeit understudied. Here, we investigated the effects of specific carotenoids on a wide range of breast cancer cell lines, and found that among several carotenoids (including β-carotene, lutein, and astaxanthin), lutein significantly inhibits breast cancer cell growth by inducing cell-cycle arrest and caspase-independent cell death, but it has little effect on the growth of primary mammary epithelial cells (PmECs). Moreover, lutein-mediated growth inhibition of breast cancer cells is quantitatively similar to that induced by chemotherapeutic taxanes, paclitaxel and docetaxel, and exposure to lutein plus taxanes additively inhibits breast cancer cell growth. Analysis of mechanisms showed that lutein treatment significantly increases the intracellular reactive oxygen species (ROS) production in triple-negative breast cancer (TNBC) cells, but not in normal PmECs. Lutein-induced growth inhibition is also attenuated by the radical oxygen scavenger N-acetyl cysteine, suggesting a role for ROS generation in the growth inhibitory effect of lutein on TNBC cells. Additionally, we found that the p53 signaling pathway is activated and HSP60 levels are increased by lutein treatment, which may contribute partly to the induction of growth inhibition in TNBC cells. Our findings show that lutein promotes growth inhibition of breast cancer cells through increased cell type-specific ROS generation and alternation of several signaling pathways. Dietary lutein supplementation may be a promising alternative and/or adjunct therapeutic candidate against breast cancer.
Highlights
Breast cancer remains the second leading cause of cancer-related death and the most frequently diagnosed cancer in American women between the ages of 20 and 59, with over 233,000 new cases and 40,000 deaths annually [1]
To determine the effects of specific carotenoids on human breast cancer cells, we initially investigated the anti-proliferative effect of three carotenoids on the growth of human breast cancer cell lines (MCF-7 [estrogen receptor (ER)/progesterone receptor (PR)+ HER2− ] and MDA-MB-468 [triple-negative]), and normal primary human mammary epithelial cells (PmECs)
MDA-MB-468 cells, we examined lutein-inducible cellular reactive oxygen species (ROS) generation in cells pretreated with the ROS scavenger, N-acetyl cysteine (NAC)
Summary
Breast cancer remains the second leading cause of cancer-related death and the most frequently diagnosed cancer in American women between the ages of 20 and 59, with over 233,000 new cases and 40,000 deaths annually [1]. It is the leading cause of cancer deaths in women. Metastatic breast cancer has had a 5-year relative survival rate under 25% [1]. It is a multistep disease involving genetic and environmental factors [2]. Expression of the Molecules 2018, 23, 905; doi:10.3390/molecules23040905 www.mdpi.com/journal/molecules
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