Antitumor potential of sanguinarine: molecular mechanisms and emerging role in targeted cancer therapy

Abstract

Intoduction. Conventional chemotherapy is often limited by primary and secondary tumor resistance, systemic toxicity, and reduced efficacy in advanced disease stages. These limitations have increased interest in natural compounds with antitumor activity. Sanguinarine (SAN), a plant-derived benzophenanthridine alkaloid, has emerged as a promising anticancer agent, demonstrating significant efficacy in multiple preclinical cancer models. Material and methods. This review analyzed 30 scientific articles published after 2015 from PubMed and Google Scholar, focusing on the anticancer potential and molecular mechanisms of natural compounds, particularly SAN. Results. SAN modulates key intracellular signaling axes, including phosphoinositide-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB), leading to inhibition of cell proliferation and reduction of tumor invasive potential. Suppression of these pathways results in cell-cycle arrest and inhibition of epithelial–mesenchymal transition (EMT), a process essential for metastasis and tumor progression. SAN can induce apoptosis by regulating the expression of pro- and anti-apoptotic proteins and activating caspases, while also stimulating autophagy, thereby promoting the elimination of resistant tumor cells. In addition, it enhances intracellular oxidative stress by increasing reactive oxygen species (ROS) beyond the tolerance threshold of malignant cells, amplifying selective cytotoxic effects. SAN also exhibits immunomodulatory activity through regulation of inflammatory mediators and transcription factors involved in cancer-associated chronic inflammation. It demonstrates synergistic potential when combined with conventional cytostatic agents, potentially enhancing antitumor efficacy while reducing required doses and systemic toxicity. Furthermore, SAN may increase tumor sensitivity to chemotherapy by interfering with molecular mechanisms of treatment resistance and by influencing epigenetic regulation processes such as DNA methylation/demethylation and histone deacetylation. Conclussions. In conclusion, SAN exerts multimodal antitumor effects through induction of oxidative stress, inhibition of proliferative signaling pathways, interference with DNA repair, and activation of multiple programmed cell death pathways. These findings highlight its potential integration into innovative targeted cancer therapy strategies.