Salidroside Regulates Energy Metabolism Reprogramming to Suppress Tumor Proliferation: Mechanisms and Therapeutic Implications

Salidroside, a phenylethanol glycoside and principal bioactive constituent of Rhodiola rosea, has emerged as a promising multi-target anti-tumor agent with significant effects on cancer energy metabolism. This review summarizes and analyzes the mechanisms it uses to reprogram tumor energy metabolism. Recent studies show that it upregulates the tumor suppressor miR-1343-3p in gastric cancer, which in turn targets two distinct metabolic axes: the OGDHL/PDHB–pyruvate axis, which impairs pyruvate oxidative decarboxylation and tricarboxylic acid cycle flux, and the ACOT11/FFA axis, which disrupts fatty acid hydrolysis and lipid-derived energy production. Both pathways are likely to converge at the reduction in acetyl-CoA, decreasing ATP synthesis and lowering the energy supply essential for rapid tumor proliferation. Furthermore, salidroside inhibits glycolysis through regulating STAT3/c-Myc, SLC7A11/cystine/GSH/GPX4, and PI3K/Akt/mTOR signaling pathways and sensitizes cancer cells to ferroptosis via regulating lipid metabolism and iron homeostasis. In vivo and in vitro studies indicate that salidroside possesses broad anti-tumor activity against a number of malignancies. This review synthesizes the findings from the past decade, providing a framework for understanding the multi-targeted inhibitory effects of salidroside on tumor metabolism and the challenges for clinical translation.