Ginsenoside Rh2 reverses cyclophosphamide-induced immune deficiency by regulating fatty acid metabolism.
J Leukoc Biol. 2019 Jun 18. Epub 2019 Jun 18. PMID: 31211478
Ginsenoside Rh2 (G-Rh2) has well-established potent antitumor activity; yet, the effects of G-Rh2 on immune and metabolism regulation in cancer treatment, especially non-small cell lung cancer (NSCLC) remain unclear. We showed that G-Rh2 had a synergistic antitumor effect with cyclophosphamide (CY) on mice with NSCLC, and improved the immune deficiency caused by CY. Consistently, G-Rh2 exhibited no inhibitory effect on tumor growth of T cells-deficient nude mice. Furthermore, G-Rh2 treatment triggered the oxidative decomposition of fatty acid (FA), suppressed FA synthesis, increased ketone level, and decreased glucocorticoid (CORT) secretion. G-Rh2 significantly down-regulated the expression of fatty acid synthase (FASN). Of note, in liver-specific FASN knockout mice G-Rh2 failed to show the same immune enhancement effects. Further mechanistic exploration revealed that G-Rh2 suppressed the expression and nuclear translocation of sterol regulatory element binding protein 1 (SREBP-1), and disturbed the SREBP-1-FASN interaction in vitro.