Caffeic acid phenethyl ester and its micro- and nanoformulations with anticancer activities

Caffeic acid phenethyl ester (CAPE), is the major phenolic compound of propolis. Several studies have highlighted its numerous pharmacological properties. CAPE displays antioxidant, anti-inflammatory, antiviral, antimicrobial, immunomodulatory, neuroprotective, cardioprotective hepatoprotective and anticancer effects. Its anticancer effects have been demonstrated both in-vitro and in-vivo on breast cancer, colon cancer, non-small cell lung cancer, oral cancer, prostate cancer cells, glioma cells, human head and neck squamous carcinoma cells, ovarian cancer, fibrosarcoma and neuroblastoma. Despite its promising pharmacological properties, its clinical application is hampered by its poor water solubility, poor bioavailability and heat-sensitivity. The encapsulation of CAPE in innovative Drug Delivery Systems (DDS) has been successfully proposed as a competitive strategy to overcome these limitations. The review summarizes the synthesis and biosynthesis of CAPE, the sources and the extraction processes, the mechanisms underlying its anticancer activity and a broad overview of the DDS applied for addressing and improving its activity in vitro and in vivo.