Guggulsterone, a Classical Lipid‐Lowering Phytosteroidal FXR Antagonist, as a Modulator of Lipid Signaling and Metabolic Reprogramming in Cancer

Dysregulated lipid metabolism fuels cancer progression through enhanced lipogenesis, cholesterol synthesis, and fatty acid oxidation. Herbal bioactives provide multi‐targeted molecular interventions capable of restoring lipid homeostasis while minimizing toxicity. Guggulsterone (GS), a plant‐derived steroidal compound from Commiphora mukul , exemplifies this paradigm by modulating key regulators such as ATP citrate lyase (ACLY), acetyl‐CoA carboxylase (ACC), farnesoid X receptor (FXR), and AMP‐activated protein kinase (AMPK). Through these actions, it suppresses oncogenic lipid signaling, reprograms the tumor microenvironment, and enhances apoptotic sensitivity. This article outlines the molecular underpinnings of GS's lipid‐lowering and antitumor effects, emphasizing its potential as a pharmacological scaffold for metabolic reprogramming in cancer.