Selective Carotenoid Growth Inhibition in Breast Cancer: Independence of Hormonal Sensitivity

Abstract

BackgroundCarotenoid intake has been associated with ↓ed cancer risk, including breast cancer. We tested if specific carotenoids inhibit cancer cell proliferation or induce apoptosis and interaction with chemotherapeutic agents.MethodsHormone sensitive and triple negative breast cancer lines and immortalized breast cells were treated with carotenoids (β‐carotene, lycopene [LYC], lutein [LUT] or astaxanthin; 0.5‐2.0 µM) singly or in combination with taxanes. Cell proliferation was analyzed by MTT and EdU assays; intracellular ROS, cell cycle and apoptosis were assayed by flow cytometry. RT‐PCR arrays were used to evaluate gene expression ± carotenoid exposure. Carotenoid‐drug combinatorial effects were determined using the Chou‐Talalay method.ResultsLUT and LYC significantly ↓ed cancer cell proliferation (threshold, < 0.5µM) with little dose‐dependency; β‐carotene and astaxanthin had no significant effects. LUT‐, LYC‐mediated growth inhibition was similar to that induced by taxanes. LUT + taxane synergistically inhibited cancer cell proliferation. LUT also ↑ed intracellular ROS and G1 arrest and expression of apoptosis‐related genes.ConclusionLUT and LYC inhibit breast cancer cell growth independent of cell hormone receptor status and additively‐synergistically with taxanes. These carotenoid‐mediated effects appear to involve inducing cell cycle arrest and increasing apoptosis. LUT (best known for effects on eye and brain health) and LYC may be important adjuncts to breast cancer chemotherapy.