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

Abstract

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 associated 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 (β-carotene, crocin, fucoxanthin, astaxanthin), β-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). β-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 β-carotene involves the JNK intracellular pathway, and this carotenoid was able to enhance the anti-proliferative effect of doxorubicin. Importantly, β-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

β-carotene presents potential as co-adjuvant to doxorubicin for triple-negative breast cancer treatment.