Anticancer and Anti-Inflammatory Potential of Betalains: A Systematic Review on Preclinical Studies.

Betalains, water-soluble pigments from beetroot and other Caryophyllales plants, have shown promising anticancer and anti-inflammatory properties, though systematic evaluations remain limited. This review synthesized preclinical in vitro and in vivo evidence on betalains' bioactivity and mechanisms. Literature searches (2015-2025) across PubMed, ScienceDirect, Wiley Online Library, and Taylor & Francis identified 481 studies, with 25 meeting inclusion criteria under PRISMA guidelines. The risk of bias was assessed using multiple tools. The review has been registered in PROSPERO under ID 1172411. Findings indicate that betalains inhibit cancer cell viability and proliferation, including IC50 values of 64 to 107 μg/mL in colorectal cancer cell lines, induce apoptosis via caspase activation, increase G2/M phase arrest to 49.6% in A549 lung cancer cells, reduce oral squamous cell carcinoma viability from 89% to 50%, and regulate genes such as p53, Bax, and Bcl-2. Anti-inflammatory effects included suppression of NF-κB signaling and reduction of TNF-α, IL-6, COX-2, and iNOS, alongside enhanced antioxidant defenses. Risk of bias was generally low. Collectively, betalains emerge as safe, food-derived compounds with potential for cancer and inflammation management. However, well-designed clinical trials remain essential to establish efficacy and therapeutic applications in humans.