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Carotenoid Lutein Selectively Inhibits Breast Cancer Cell Growth and Potentiates the Effect of Chemotherapeutic
Xiaoming Gong1, Joshua R Smith2, Haley M Swanson3
1Department of Pediatrics, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA. Xiaoming.gong@ttuhsc.edu.
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.
Insights
Lutein, a dietary carotenoid, inhibits breast cancer cell growth by inducing cell death and cell cycle arrest. It shows promise as a potential therapeutic agent against breast cancer.
Area of Science:
- Oncology
- Nutritional Science
- Cell Biology
Background:
- Dietary carotenoids are investigated for their potential role in reducing breast cancer risk.
- The anti-cancer effects of carotenoids, including lutein, require further investigation due to controversial findings.
Purpose of the Study:
- To investigate the specific effects of carotenoids, particularly lutein, on breast cancer cell lines.
- To elucidate the mechanisms underlying lutein's anti-cancer activity and its potential therapeutic applications.
Main Methods:
- Testing several carotenoids (β-carotene, lutein, astaxanthin) on various breast cancer cell lines and primary mammary epithelial cells (PmECs).
- Assessing lutein's effects in combination with taxanes (paclitaxel, docetaxel).
- Analyzing intracellular reactive oxygen species (ROS) production, p53 signaling pathway activation, and HSP60 levels.
Main Results:
- Lutein significantly inhibited breast cancer cell growth, inducing cell-cycle arrest and caspase-independent cell death, with minimal impact on normal PmECs.
- Lutein's growth inhibition was comparable to taxanes, and combined treatment showed additive effects.
- Lutein increased ROS production in triple-negative breast cancer (TNBC) cells, an effect attenuated by N-acetyl cysteine, suggesting a role for ROS.
- Lutein activated the p53 signaling pathway and increased HSP60 levels in TNBC cells.
Conclusions:
- Lutein effectively inhibits breast cancer cell growth via cell type-specific ROS generation and modulation of signaling pathways like p53 and HSP60.
- Lutein demonstrates potential as an alternative or adjunct therapeutic strategy for breast cancer, particularly TNBC.
- Dietary lutein supplementation may offer a promising approach for breast cancer prevention and treatment.
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