Natural bioactives in the suppression of EMT: A Focus on female cancer therapeutics

Cancer progression and mortality are predominantly caused by tumour invasion, metastatic dispersion, and the evolution of therapeutic resistance. Among the complex molecular mechanisms that contribute to these processes, epithelial-mesenchymal transition has emerged as a critical regulator of tumour cell plasticity, allowing epithelial cancer cells to acquire mesenchymal characteristics associated with enhanced migration, invasion, stemness, immune evasion, and resistance to anticancer therapies. Female malignancies, such as breast, ovarian, cervical, and endometrial cancers, have widespread EMT activation, which contributes considerably to aggressive tumour behaviour and poor clinical outcomes. EMT is controlled by signalling cascades such as Wnt/β-catenin, PI3K/AKT, TGF-β, Notch, Hedgehog, and NF-κB. These pathways regulate transcription factors like SNAIL, SLUG, TWIST, and ZEB1/2, leading to loss of epithelial markers and acquisition of invasive mesenchymal traits. Despite breakthroughs in targeted medicines, therapeutic resistance and tumour recurrence remain significant hurdles, emphasizing the need for new methods capable of influencing EMT-driven tumour growth. Natural bioactive compounds have recently received a lot of interest as possible anti-cancer medicines due to their multi-targeted methods, low toxicity profiles, and capacity to regulate critical biochemical pathways implicated in EMT. Phytochemicals such flavonoids, polyphenols, alkaloids, and terpenoids have been shown to reverse EMT, reduce metastatic behaviour, limit cancer stem cell features, and improve therapeutic sensitivity by modulating EMT-associated signalling networks. This review provides a detailed overview of the molecular processes that control EMT in various female malignancies, as well as an examination of the therapeutic potential of natural bioactive chemicals as EMT-targeting therapies. Furthermore, it emphasizes the emerging role of natural compounds as promising candidates for preventing metastasis and improving therapeutic outcomes in female cancer management.