Moringa oleifera in Breast Cancer: Targeting ROS, p53, and VEGF Pathways through Phytochemical Synergy

Abstract

Background: Breast cancer remains a leading cause of cancer-related mortality worldwide, with dysregulation of reactive oxygen species (ROS), p53 tumour suppressor pathway, and vascular endothelial growth factor (VEGF)-mediated angiogenesis contributing to tumour progression, metastasis, and therapeutic resistance. Natural products like Moringa oleifera (MO), a nutrient-rich medicinal plant, exhibit promising anticancer properties through its diverse phytochemicals, including flavonoids, isothiocyanates, and phenolics, which may act synergistically to target these pathways.

Objective: This review evaluates the mechanistic role of M. oleifera in modulating ROS, p53, and VEGF pathways in breast cancer, emphasising phytochemical synergies for enhanced therapeutic efficacy.

Methods: A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science databases using keywords such as "Moringa oleifera," "breast cancer," "ROS," "p53," "VEGF," and "phytochemical synergy," covering studies from 2000 to October 2025. Inclusion criteria focused on preclinical in vitro/in vivo evidence and computational modeling; 45 relevant articles were analyzed.

Key Findings: MO extracts and isolated compounds (e.g., glucomoringin, quercetin) reduce ROS accumulation in breast cancer cells (e.g., MCF-7, MDA-MB-231) by activating Nrf2 and antioxidant enzymes, mitigating oxidative stress-induced proliferation. They restore p53 function via upregulation of p53-Bax apoptosis cascades, inducing cell cycle arrest and tumor regression in xenograft models. Anti-angiogenic effects involve downregulation of HIF-1α-VEGF signaling, decreasing vascularization and metastasis potential. Synergistic interactions, such as flavonoids enhancing isothiocyanate bioavailability, amplify these effects, outperforming single agents in polyherbal formulations.