Ursolic and Oleanolic Acids as Multitarget Modulators of Cancer Hallmarks: Molecular Mechanisms and Emerging Evidence on Autophagy

Cancer remains a major global health challenge, and chemoresistance continues to limit the efficacy of antineoplastic therapies. Pentacyclic triterpenes, such as oleanolic acid (OA) and ursolic acid (UA), have attracted significant interest because of their diverse biological activities, including anticancer effects. UA and OA influence several processes associated with cancer development and progression, including tumor cell proliferation, growth-suppressive signaling, immune and inflammatory responses, migration and invasion, apoptosis, and cellular metabolism. Their biological activity also involves autophagy, a process closely interconnected with several cancer hallmarks and particularly relevant because of its context-dependent functions in tumor biology. While autophagy contributes to cellular homeostasis and can suppress early tumor development, established tumors can exploit this process to promote survival and adaptation to metabolic and therapeutic stress. This review critically examines the anticancer effects of UA and OA within the framework of the hallmarks of cancer, with particular emphasis on the molecular mechanisms underlying autophagy and its contribution to the cellular responses induced by these triterpenes. Evidence from cancer cell lines and animal models indicates that UA and OA affect interconnected signaling pathways involved in cancer-associated processes, while autophagy can either enhance or counteract their experimental anticancer effects, depending on the cellular and experimental context. This dual behavior provides a mechanistic basis for understanding the context-dependent activity of UA and OA and for exploring strategies that integrate autophagy modulation into future evaluations of these compounds as multitarget anticancer agents.