Phytochemicals as Anticancer Agents: Investigating Molecular Pathways from Preclinical Research to Clinical Relevance
Sarah Jane Monica, Deevena Jemima, D. Esther Lydia, Priyadarshini Selvaraju, Mary Anne Preetha, Emi Grace Mary Gowshika Rajendran
Abstract
Cancer remains a significant global health threat, with annual deaths projected to reach 16.2 million by 2040. Phytochemicals in different botanical sources offer promising cancer preventive strategies due to their unique biological activities, affordability, ease of use, and relatively lower toxicity. This review compiles the anticancer activities of phytochemicals in various plant-based food groups as demonstrated in preclinical models and human studies. A literature survey was performed in various research databases such as Google Scholar, PubMed, Scopus, and Web of Science to identify relevant peer-reviewed publications, including original research and review articles published between 2018 and 2025. Phytochemicals such as flavonoids, phytosterols, phenolic acids, carotenoids, and stilbenes, exert anticancer effects through anti-angiogenesis, metastasis, cell cycle arrest, apoptosis, and modulating cell signalling pathways like PI3K/Akt/mTOR/P70S6K pathway, MAPK/ERK, NF-κB, and Wnt/β-catenin as documented in in vitro and animal studies. Prospective human studies show that phytochemicals in different food groups, such as whole grains, nuts and seeds, fruits and vegetables, and tea extracts, exhibit anticancer effects. One significant challenge with phytochemical use is their poor bioavailability. Although numerous experimental studies have explored strategies to enhance phytochemical bioavailability, such as nano formulations, co-administration with bioenhancers, and structural modifications, clinical research on the pharmacokinetics, potential nutrient interactions, optimal dosing, and long-term safety of isolated or enriched phytochemicals remains limited.