Cinnamaldehyde From Cinnamon as a Food‐Derived Bioactive: Phytochemistry, Anticancer Mechanisms, Bioavailability, Nanoformulation and Safety

ABSTRACT Cinnamaldehyde (CA), a bioactive compound derived from Cinnamomum species, has gained attention for its potential anticancer properties. Preclinical evidence suggests that CA exerts antitumor effects through multiple mechanisms, including the induction of apoptosis, modulation of redox homeostasis, inhibition of cell proliferation, and disruption of key signaling pathways such as PI3K/Akt/mTOR and MAPK/ERK. Its selective cytotoxicity toward cancer cells, with minimal effects on normal cells, further supports its therapeutic relevance. This review evaluated current evidence regarding the anticancer activity of CA, with a focus on its molecular mechanisms, structure–activity relationships, semisynthetic derivatives, and potential for combinatorial therapy. Relevant experimental and preclinical studies were examined to assess CA's efficacy in various cancer types, its pharmacokinetic limitations, and strategies for improved delivery, including nanoparticle and liposomal formulations. Findings indicate that CA affects several hallmarks of cancer, including apoptosis resistance, sustained proliferation, and metastasis. Enhanced anticancer activity has been reported when CA is used in combination with standard chemotherapeutic agents or other natural compounds. Nanotechnological approaches have demonstrated potential in overcoming CA's low bioavailability and rapid metabolism. CA shows promise as a multitargeted, low‐toxicity compound suitable for adjuvant cancer therapy. Further investigation, particularly through clinical trials and advanced delivery systems, is required to confirm its efficacy and support clinical application.