Targeting Cancer Signaling Pathways With Plant Sterols: Emerging Roles of Stigmasterol, Campesterol, and β‐Sitosterol

Plant sterols are naturally occurring tetracyclic triterpenes that serve as essential structural components of plant cell membranes. Structurally similar to cholesterol, these bioactive compounds have gained considerable attention for their diverse therapeutic properties, particularly their anticancer potential. Among them, stigmasterol, campesterol, and β-sitosterol are the most abundant and well-studied phytosterols known for their multifaceted roles in tumor suppression and apoptosis induction. They modulate several oncogenic signaling pathways, including PI3K/AKT/mTOR, JAK/STAT, NF-κB, and Wnt/β-catenin, thereby inhibiting cancer progression. Their anticancer activities involve mechanisms such as cell cycle arrest, activation of mitochondria-mediated apoptosis, inhibition of angiogenesis, and suppression of metastasis. Specifically, stigmasterol promotes apoptosis by upregulating Bax and p53, downregulating Bcl-2, and inhibiting angiogenic and JAK/STAT signaling. Campesterol induces cancer cell death through mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress, enhancing the efficacy of chemotherapeutic agents. β-sitosterol inhibits proliferation, triggers cell cycle arrest, regulates apoptotic proteins, and suppresses metastasis while overcoming drug resistance. Despite extensive individual studies, a comprehensive review summarizing their collective anticancer mechanisms is lacking. This work bridges that gap by systematically analyzing literature from the past 10 years across major databases, including Google Scholar, ScienceDirect, Scopus, Wiley Online Library, and Web of Science. Evidence from preclinical, clinical, and pharmacological studies was critically evaluated to highlight the therapeutic potential of these sterols in tumor suppression and apoptosis, providing a consolidated foundation for future drug discovery and development. The unique contribution of this review lies in proposing a comparative mechanistic framework for stigmasterol, campesterol, and β-sitosterol, integrating their multi-targeted actions across key oncogenic signaling pathways to highlight their collective potential in anticancer therapy.