# Cyclamen persicum Bulb Extract Modulates NF-κB, Oxidative Stress, and Apoptotic Pathways in Triple-Negative Breast Cancer

## TL;DR

This study shows that an extract from Cyclamen persicum bulbs has strong anticancer effects, especially in triple-negative breast cancer cells, by reducing cell growth and promoting cell death.

## Contribution

The study identifies a new natural source with potential anticancer properties and explores its mechanisms in triple-negative breast cancer.

## Key findings

- Cyclamen persicum extract reduced cell viability and proliferation in MDA-MB-231 TNBC cells.
- The extract modulated NF-κB signaling and induced apoptosis while decreasing cancer cell migration and invasion.
- Anticancer effects were also observed in prostate, pancreatic, and intestinal cancer cell lines.

## Abstract

Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with poor prognosis and limited targeted therapeutic options. Natural products, rich in bioactive phytochemicals, represent a potential source of novel anticancer agents. This study examined the phytochemical profile and anticancer activity of an ethanolic bulb extract of Cyclamen persicum (CPE), with a primary focus on TNBC. Methods: The phytochemical composition of CPE was analyzed by liquid chromatography–mass spectrometry (LC–MS). Antioxidant activity was evaluated using DPPH radical scavenging assay. The anticancer effects of CPE were assessed mainly in MDA-MB-231 TNBC cells using MTT cell viability assays, Ki-67 immunoblotting, Western blot analysis of signaling proteins, wound healing migration assays, Matrigel invasion assays, adhesion assays and cell–cell aggregation assays. Antiproliferative activity was also examined in 22RV1 (prostate), Capan-2 (pancreatic), and HCT116 (intestinal) cancer cell lines using MTT assays. Results: LC–MS analysis indicated that the extract contains multiple polyphenolic and organic acid constituents commonly associated with bioactivity. Consistent with this profile, CPE demonstrated strong antioxidant activity. In MDA-MB-231 cells, CPE significantly reduced cell viability and proliferation, accompanied by decreased Ki-67 expression. Treatment was associated with modulation of proteins involved in proliferative and survival signaling, induction of apoptosis-related markers, and reduced migratory and invasive capacities. CPE also promoted cell–cell homotypic aggregation, suggesting a shift toward a less aggressive phenotype. These effects were associated with reduced phosphorylation of p65, indicating possible modulation of NF-κB signaling. Additionally, CPE decreased proliferation in 22RV1, Capan-2, and HCT116 cancer cell lines. Conclusions: Collectively, these findings indicate that C. persicum bulb extract exerts multimodal anticancer effects in vitro, particularly in TNBC cells, and highlights its potential as a source of bioactive compounds warranting further mechanistic and translational investigation.