What question did this study set out to answer?

To explore the diverse mechanisms by which ferulic acid exerts its chemotherapeutic effects across various cancers.

April 22, 2026Open Access

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

Key Points

To explore the diverse mechanisms by which ferulic acid exerts its chemotherapeutic effects across various cancers.
Review of existing evidence on the pharmacological activities and mechanisms of ferulic acid.
Analysis of ferulic acid's effectiveness against 16 different cancer types.
Investigation of synergistic effects with other compounds and treatments.
Ferulic acid demonstrated effectiveness through various mechanisms including apoptosis and signaling pathways.
Nanoformulation improved ferulic acid's solubility and delivery, enhancing its anticancer properties.
It showed potential in reversing resistance to standard chemotherapies and combined well with other treatments.

Abstract

ABSTRACT 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.

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