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

Abstract

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.