Deciphering the Chemotherapeutic Mechanism of Ferulic Acid: Insight Into the Role Against Multiple Human Cancers.

Extensive research continues to address the challenges of developing standard cancer drugs. However, until more effective standard drugs are developed, ferulic acid (FA) may be a potential option for controlling the symptoms of cancer patients. According to our review, FA is available in natural sources and has flexible structures that possess diverse pharmacological activities. FA is effective against 16 different cancer types and has been validated in cell culture, preclinical, and clinical models. Chemotherapeutics activities of FA are regulated through varieties of mechanisms, including targeting signaling pathways, such as AKT/PI3K/mTOR/ERK/STAT NF-κB; apoptosis, such as FAS/FASL, TRADD, Bcl2, Bax, Caspases, and PARP; metastasis, such as MMPs(1,2,9), Wnt/-β catenin, angiogenesis (E&N Cadherin, vimentin, Snail, and Slug), cell proliferation (cyclin D1, E1, and CDKs(2,4,6)), inflammatory molecules (TNF-α, NF-κB,1α, IL-10, IL-8, and IL-6), regulating tumor suppressor genes (p-RB, p21, and p53), autophagy (LC3-II, p62, Beclin1, and Atg12-Atg5), glycolysis (lncRNA 495810 and PKM2), heat shock protein (Hsp60, Hsp70, and Hsp90), and some nonspecific pathways, such as oncogene suppression and antioxidant efficacies. Nanoformulation of FA increased its solubility, stability, and bioavailability, thereby enabling controlled release and making FA more effective against cancer. Additionally, FA exerted synergistic effects with other natural compounds, vitamins, radiotherapy, and chemotherapies, and reversed resistance to existing chemotherapies via diverse mechanisms, including targeting multidrug resistance proteins, apoptosis, reactive oxygen species production, hypoxia, microRNA, the β-catenin pathway, oncogene activation, and sensitizing chemotherapies and radiotherapies. Given that FA has validated the experimental model and demonstrated preliminary efficacy, these findings suggest a possible supportive role for phytochemicals pending the development of fully effective pharmaceutical therapies.