Anticancer Potential of Oleandrin: Preclinical Mechanisms, Botanical Origins, and Pharmacokinetic Insights

Oleandrin (OLD) is a lipid-soluble cardiac glycoside derived mainly from the leaves of Nerium oleander (Apocynaceae), traditionally used in herbal medicine. Among the various parts of the plant, the leaves contain the highest concentration of OLD. Red-flowered varieties contain higher levels of cardiac glycosides. Although Thevetia peruviana (yellow oleander) belongs to the same family, it does not produce OLD. Recent studies show that OLD has significant anticancer potential against various cancers such as breast, prostate, lung, colon, pancreatic, endometrial cancers, melanoma, and osteosarcoma. It works by inducing apoptosis (programmed cell death) via caspase activation, arresting the cell cycle, reducing oxidative stress, and lowering mitochondrial membrane potential. These actions are regulated by key signaling pathways including Wnt/β-catenin, phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-kappa B (PI3K/Akt/NF-κB), and extracellular signal-regulated kinase (ERK). Pharmacokinetic studies reveal that OLD is rapidly absorbed through the oral mucosa and gastrointestinal tract, crosses the blood-brain barrier, and has a half-life of about 2.3 hours. It is mainly metabolized in the liver and intestine, and excreted mostly through feces (66%) and partly through urine (8%). Due to its strong anticancer mechanisms, OLD shows promise as a novel anticancer agent. However, further in vivo studies and clinical trials are necessary to confirm its therapeutic efficacy and safety in humans. Future research should also focus on optimizing its pharmacokinetic properties and minimizing toxicity to enable its transition from experimental models to clinical application.