Dual-mechanism of phytochemicals in cancer therapy: synergistic anti-angiogenic potency in cancer and proangiogenic impact against chemotherapy-induced cytotoxicity in vital organs

Abstract

Angiogenesis is essential for tumor growth and metastasis, yet physiological angiogenesis is equally critical for tissue repair and endothelial homeostasis. This creates a therapeutic dilemma: suppressing tumor neovascularization without impairing vascular integrity in healthy organs, particularly under cytotoxic chemotherapy. This review summarizes key pro- and anti-angiogenic pathways that regulate tumor vascularization, highlights limitations of current anti-angiogenic therapies (including resistance and delivery barriers), and synthesizes evidence that selected phytochemicals exert context-dependent angiogenesis modulation. Specifically, many compounds inhibit pathological tumor angiogenesis (via VEGF/HIF-1α/NF-κB/MMP-related signaling) while supporting endothelial defense and microvascular recovery in non-cancerous tissues through antioxidant, anti-inflammatory, and anti-apoptotic pathways (e.g., Nrf2/HO-1). Finally, we discuss translational requirements—bioavailability, standardization, dosing windows, and safety—to inform rational adjunct development and future biomarker-driven clinical trials.