Ferulic acid-mediated modulation of apoptotic signaling pathways in cancer

Ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA), a hydroxycinnamic acid derived from various seeds, nuts, leaves, and fruits, exists in a free form as well as is covalently conjugated with polysaccharides, glycoproteins, polyamines, lignin, and hydroxy fatty acids of plant cell walls. It exhibits a variety of pharmacological effects, such as antioxidant, anti-inflammatory, vasodilatory, antithrombotic, antimicrobial, anti-allergic, antiviral, hepatoprotective, and anticancer activities. FA induces the expression of cell cycle-related proteins, such as p53 and p21, and reduces cyclin D1 and cyclin E levels. Moreover, FA triggers apoptosis and autophagic cell death depending on intracellular reactive oxygen species production in various cancer cell lines. The potential apoptotic action of FA is mediated by altered expression of procaspase-3, procaspase-8, procaspase-9, poly (ADP ribose) polymerase, Bcl-2, and Bax. It blocks the activation of both the canonical Smad and noncanonical extracellular-signal-regulated kinase/Akt (protein kinase B) pathways in various cancer cells. However, due to low solubility and permeability, its availability to biological systems is limited. Therefore, encapsulation of FA into chitosan tripolyphosphate nanoparticles may enhance its cytocompatibility, solubility, and anticancer potential. The nanohybrids of FA and double layered hydroxide exhibit cellular delivery properties of intercalated molecules on cancer cell lines. This chapter summarizes the anticancer efficacy of FA with an emphasis on the role of apoptosis, and underlying molecular mechanisms involving various signaling pathways in tumor cells.