A Standardized Extract of Petasites hybridus L., Containing the Active Ingredients Petasins, Acts as a Pro-Oxidant and Triggers Apoptosis through Elevating of NF-κB in a Highly Invasive Human Breast Cancer Cell Line

A Standardized Extract of Petasites hybridus L., Containing the Active Ingredients Petasins, Acts as a Pro-Oxidant and Triggers Apoptosis through Elevating of NF-κB in a Highly Invasive Human Breast Cancer Cell Line

Sonia Apostolova^1,*, Tsvetelina Oreshkova², Veselina Uzunova¹, Irina Georgieva¹, Liliana Maslenkova¹, Rumiana Tzoneva^1,*

Show Less

¹ Laboratory of Transmembrane Signaling, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria

² Institute of Biology and Immunology of Reproduction “Acad. Kiril Bratanov'', Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria

^*Correspondence: sonia_apostolova@yahoo.com (Sonia Apostolova); tzoneva@bio21.bas.bg (Rumiana Tzoneva)

Front. Biosci. (Landmark Ed) 2023, 28(6), 111; https://doi.org/10.31083/j.fbl2806111

Submitted: 6 April 2023 | Revised: 12 May 2023 | Accepted: 18 May 2023 | Published: 12 June 2023

This is an open access article under the CC BY 4.0 license.

Abstract

Background: Common butterbur (Petasites hybridus L.) is a traditional medicinal plant with numerous therapeutic properties among which is its recently uncovered anti-tumor activity. The present study aims to examine the activity of a standardized Bulgarian Petasites hybridus L. root extract, containing the active ingredients petasins, on the human breast cancer cell line MDA-MB-231 and non-cancerous MCF-10A cells. Specifically, we examined cell death, oxidative stress, and nuclear factor kappa-B (NF- $\kappa{}$ B) signaling. Methods: A standardized butterbur powdered extract containing a minimum of 15% petasins was used. A lipophilic extract was obtained from subterranean portion of the plant of Bulgarian populations of Petasites hybridus using liquid-liquid extraction after completely removing pyrrolizidine alkaloids. The induction of apoptosis and necrosis was analyzed by flow cytometry, and oxidative stress biomarkers and NF- $\kappa{}$ B were measured using enzyme-linked immunosorbent assay (ELISA). Results: Petasites hybridus L. root extract triggered apoptosis in a cancer-specific fashion and induced a moderate oxidative stress characterized by diminished glutathione (GSH) levels and elevated malondialdehyde (MDA) levels in MDA-MB-231 72 h after treatment. NF- $\kappa{}$ B levels were higher in cancer cells after treatment with IC ${}_{50}$ and IC ${}_{75}$ doses, this suggested that the NF- $\kappa{}$ B pathway was activated in response to oxidative stress leading to the induction of apoptosis. MCF-10A cells were affected to a lesser extent by the Petasites hybridus extract, and the adaptive response of their antioxidant defense system halted oxidative stress. Conclusions: Overall, these results indicate that Petasites hybridus L. root extract selectively acts as a pro-oxidant in breast cancer cells and thus represents a potential therapeutic option for cancer treatment with fewer side effects.