Molecular Mechanisms of <i>Lobelia nummularia</i> Extract in Breast Cancer: Targeting EGFR/TP53 and PI3K-AKT-mTOR Signaling via ROS-Mediated Apoptosis

Molecular Mechanisms of <i>Lobelia nummularia</i> Extract in Breast Cancer: Targeting EGFR/TP53 and PI3K-AKT-mTOR Signaling via ROS-Mediated Apoptosis

<i>Lobelia nummularia</i> Lam. is a traditional medicinal herb of which the anticancer mechanisms remain largely unexplored. Here, we demonstrated that its ethanolic extract (LNE) exerts potent anti-breast cancer activity by inducing ROS-dependent mitochondrial apoptosis in MDA-MB-231 ce...

Full description

Saved in:
Bibliographic Details
Main Authors: Fahu Yuan, Yu Qiao, Zhongqiang Chen, Huihuang He, Fuyan Wang, Jiangyuan Chen
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Current Issues in Molecular Biology
Subjects:
triple-negative breast cancer (TNBC)
natural products
luteolin
apigenin
oxidative stress
network pharmacology
Online Access:https://www.mdpi.com/1467-3045/47/7/546
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:<i>Lobelia nummularia</i> Lam. is a traditional medicinal herb of which the anticancer mechanisms remain largely unexplored. Here, we demonstrated that its ethanolic extract (LNE) exerts potent anti-breast cancer activity by inducing ROS-dependent mitochondrial apoptosis in MDA-MB-231 cells, a mechanism confirmed via rescue experiments with the antioxidant N-acetylcysteine (NAC). This pro-apoptotic program is driven by a dual mechanism: potent suppression of the pro-survival EGFR/PI3K/AKT signaling pathway and simultaneous activation of the TP53-mediated apoptotic cascade, culminating in the cleavage of executor caspase-3. Phytochemical analysis identified numerous flavonoids, and quantitative HPLC confirmed that key bioactive compounds, including luteolin and apigenin, are substantially present in the extract. These mechanisms translated to significant in vivo efficacy, where LNE administration suppressed primary tumor growth and lung metastasis in a 4T1 orthotopic model in BALB/c mice. Furthermore, a validated molecular docking protocol provided a plausible structural basis for these multi-target interactions. Collectively, this study provides a comprehensive, multi-layered validation of LNE’s therapeutic potential, establishing it as a mechanistically well-defined candidate for natural product-based anticancer drug discovery.
ISSN:1467-3037
1467-3045

Similar Items