Echinacea Angustifolia DC Extract Induces Apoptosis and Cell Cycle Arrest and Synergizes with Paclitaxel in the MDA-MB-231 and MCF-7 Human Breast Cancer Cell Lines

Abstract

Background

Echinacea spp. displays different biological activities, such as antiviral, immunomodulatory, and anticancer activities. Currently, high sales of hydroalcoholic extracts of Echinacea have been reported; hence, the importance of studies on Echinacea.

Aim

To establish the effects of Echinacea angustifolia DC extract obtained with ethyl acetate (Ea-AcOEt) in breast cancer cell lines.

Methods

Cytotoxicity, cell cycle arrest, and cell death were evaluated. Besides, the safety of the extract, as well as its effect in combination with paclitaxel were investigated.

Results

The echinacoside and caffeic acid content in the Ea-AcOEt extract were quantified by HPLC, and its antioxidant activity was assessed. The Ea-AcOEt extract showed cytotoxic activity on breast cancer MDA-MB-231 cells (IC₅₀ 28.18 ± 1.14 µg/ml) and MCF-7 cells (19.97 ± 2.31 µg/ml). No effect was observed in normal breast MCF-10 cells. The Ea-AcOEt extract induced cell cycle arrest in the G1 phase and caspase-mediated apoptosis. No genotoxicity was found in vitro or in vivo, and the extract showed no signs of toxicity or death at 2,000 mg/kg in rodents. In vitro, the combination of Ea-AcOEt extract and paclitaxel showed a synergistic effect on both cancer cell lines.

Conclusion

The Ea-AcOEt extract is a potential candidate for breast cancer treatment.

Acknowledgments

Jaramillo-Flores, Ph. D. and Ordaz-Pichardo, Ph. D., received fellowships from Comisión de Operación y Fomento a las Actividades Académicas (COFAA) and Estimulo al Desempeño de los Investigadores (EDI).

Disclosure Statement

The authors do not report any conflicts of interest.

Funding

The authors thank the Institutional Stimulus and Researcher Training Scholarship (BEIFI), SIP-IPN scholarships - Mexico [grant nos. 20170537, 20170538, 20181154, 20181163, 20195357, and 20195309) for the financial support, and Mexico for the scholarship awarded (596413) to the student Daniel Abraham Espinosa-Paredes who studied in the program of “Doctorate in Biotechnology Sciences of the National Polytechnic Institute.”

Authors’ Contribution

Espinosa-Paredes Daniel Abraham Ph.D. student in Biotechnology Sciences, practical development of the project. Cornejo-Garrido Jorge obtaining the extract and toxicological tests. Moreno-Eutimio Mario Adán establishment of molecular biology techniques to determine the mechanism of action. Martínez-Rodríguez Oswaldo Pablo carried out and analyzed the docking studies. Jaramillo-Flores María Eugenia establishment of total phenol and flavonoid content techniques and determination of antioxidant capacity and Ordaz-Pichardo Cynthia Establishment of cytotoxic activity by MTT assay and general director of the project.