Alantolactone as a Bioactive Sesquiterpene Lactone: Molecular Mechanisms and Anticancer Potential for Pharmaceutical...

Cancer remains a major global health challenge, responsible for millions of deaths each year. The limitations of current therapies, including adverse effects and drug resistance, have intensified the search for safer, more effective alternatives, particularly from natural sources. Alantolactone, a sesquiterpene lactone extracted from Inula helenium and related medicinal plants, has emerged as a promising anticancer candidate due to its diverse pharmacological actions. Although notable anticancer properties have been reported, its full therapeutic potential, mechanisms of action, and translational relevance remain insufficiently explored and scattered across the literature. This review provides a comprehensive synthesis of current evidence on alantolactone's anticancer effects. It examines its sources, phytochemical features, structure-activity relationships, bioavailability challenges, mechanistic pathways, and preclinical findings, alongside perspectives for future clinical application. Evidence shows that alantolactone modulates multiple molecular targets and signaling cascades, including NF-κB, STAT3, MAPK, and apoptotic regulators. It demonstrates strong cytotoxic activity across diverse cancer cell lines and tumor-bearing animal models. However, barriers such as low systemic bioavailability, limited pharmacokinetic profiling, and the absence of human clinical data impede its therapeutic development. Alantolactone nonetheless holds significant promise as a multi-targeted anticancer compound with encouraging preclinical outcomes. Further research is required to address pharmacological limitations and establish safety and efficacy in clinical contexts. This review highlights alantolactone's potential contribution to future cancer therapy and emphasizes the need for interdisciplinary research to support its clinical translation and formulation advancement.