The anti-proliferative effect of 0-carotene against a triple-negative breast cancer cell line is cancer cell-specific and JNK-dependent

Background: Breast cancer is a major cause of cancer-related mortality in women worldwide. Triple-negative breast cancer presents an aggressive behavior and a poor response to therapeutic. Cancer progression is asso-ciated with reprogramming of metabolic pathways for glutamine, glucose and folic acid. Methods: In this study, we characterized the antitumoral effect (effects on cell proliferation, culture growth, viability, migration, oxidative stress levels, cell cycle and apoptosis) of carotenoids on a triple-negative human breast cancer cell line (MDA-MB-231 cell line) and investigated interference with nutrient cellular uptake as a contributing mechanism.Results: Of the four tested carotenoids (0-carotene, crocin, fucoxanthin, astaxanthin), 0-carotene presented the most interesting antitumoral effect, by reducing cell proliferation, migration, viability and culture growth, inducing apoptosis and by interfering with cell cycle (S phase arrest). 0-carotene significantly increased 3H-deoxy-D-glucose uptake but did not affect neither 3H-glutamine nor 3H-folic acid uptake. Also, it did not interfere with oxidative stress levels. The anti-proliferative effect of 0-carotene involves the JNK intracellular pathway, and this carotenoid was able to enhance the anti-proliferative effect of doxorubicin. Importantly, 0-carotene did not affect cell viability, proliferation, cell cycle and migration rates of MCF-12A cells, a non-tumoral human breast epithelial cell line. Conclusion: 0-carotene presents potential as co-adjuvant to doxorubicin for triple-negative breast cancer treatment.