REVIEW article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Dual-Mechanism of Phytochemicals in Cancer Therapy: Synergistic Anti-angiogenic Potency in Cancer and Proangiogenic Impact Against Chemotherapy-Induced Cytotox-icity in Vital Organs
Deiaa E. Elsayed Abouzed 1
Nervana M. K. Bayoumy 2
Hanan Hagar 2
Safwat M. Rabea 3
Hamada Hashem 1
Hazim O. Khalifa 4
1. Sohag University, Nasser City, Egypt
2. King Saud University, Riyadh, Saudi Arabia
3. Minia University, Minya, Egypt
4. United Arab Emirates University, Al-Ain, United Arab Emirates
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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 neovas-cularization 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 require-ments—bioavailability, standardization, dosing windows, and safety—to inform rational adjunct development and future biomarker-driven clinical trials
Summary
Keywords
Angiogenesis, Antiangiogenetic therapy, chemotherapy toxicity, Cytoprotection, phytochemicals
Received
08 January 2026
Accepted
19 February 2026
Copyright
© 2026 Elsayed Abouzed, K. Bayoumy, Hagar, Rabea, Hashem and Khalifa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Hazim O. Khalifa
Disclaimer
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