Unveiling the anti-cancer properties of apigenin via targeting different molecular signatures: A Review

Apigenin, is a plant derived flavone found in parsley, celery and some spices. It has fascinated a lot of researchers because of its anti-viral, anti-bacterial, anti-inflammatory and above all its anti-cancer abilities. This review was created to understand the role of apigenin, in the prevention and treatment of cancer by targeting all hallmarks of cancer in in vitro and in vivo studies.

Various studies unfolding apigenin's role as anti-cancer agent were examined using databases like PubMed, Google scholar, Scopus and Science direct with an emphasis on its potential as an anti-proliferative, anti-apoptotic, and anti-migratory agent. Furthermore, studies that depicted epigenetic modulations and nano-based delivery were also scanned. Recent developments in nanoparticle-based delivery methods that increase apigenin's bioavailability and therapeutic effectiveness are also included.

The compiled evidence indicates that apigenin exhibits broad spectrum anticancer activity by modulating multiple cancer hallmarks, including apoptosis induction, autophagy regulation, suppression of metastasis, and inhibition of inflammatory and metabolic pathways such as GLUT1/GLUT2 mediated glucose uptake. Mechanistically, these effects are strongly linked to its epigenetic reprogramming ability, including regulation of HDACs, DNMT1, EZH2, and oncogenic miRNAs, leading to reactivation of tumor suppressor genes. Across in vitro and in vivo models, apigenin consistently demonstrates selective cytotoxicity toward cancer cells while sparing normal cells, largely through restoration of dysregulated signaling pathways. Additionally, it enhances chemosensitivity and overcomes multidrug resistance when used in combination with conventional chemotherapeutics. However, its therapeutic potential is partly limited by poor bioavailability, which is being effectively addressed through emerging nanoformulation strategies and computational (AI/bioinformatics) approaches for improved delivery and efficacy.