Updates on the Strategies to Improve the Anti-Tumor Efficacy of Ferulic Acid.

Ferulic acid, a natural phenolic phytotherapeutic, which is mainly found in plant cell walls, has attracted the attention of researchers for its multiple pharmacological properties, especially for its anti-tumor potential. As an efficient antioxidant, the compound counteracts oxidative stress and modulates key molecular pathways involved in carcinogenesis. Recent studies demonstrate that ferulic acid exerts antiproliferative, pro-apoptotic, and anti-metastatic effects in various tumor models, including colon, breast, liver, and lung cancers. Mechanistically, ferulic acid affects components of prosurvival-signaling pathways such as PI3K/Akt, MAPK, and NF-κB, and stimulates programmed cell death by diverse mechanisms, including apoptosis, autophagy and ferroptosis. Furthermore, its ability to sensitize cancer cells to chemotherapeutic drugs with low toxicity to normal cells underscores its therapeutic potential. Despite promising preclinical anti-tumor activity, low water solubility and bioavailability limit its clinical use. For this reason, several attempts, ranging from chemical derivatives to nanodevices, have been made to improve ferulic bioavailability and anti-tumor efficacy. This review highlights the most significant and recent strategies to ameliorate the anticancer ability of ferulic acid in the perspective of a clinical application.