Adenoid cystic carcinoma (ACC) is a highly aggressive neoplasm, mostly occurring in salivary glands characterized by tumor-induced angiogenesis required for invasive growth and hematogenous metastasis. Licorice has been used in Chinese folk medicine as a remedy for angiogenesis-related diseases and isoliquiritigenin (ISL) is a flavanoid isolated from licorice, with known antitumor properties. Sun et al. studied the effects of ISL on ACC-induced angiogenesis and demonstrated that ACC-induced angiogenesis is mediated by the constitutive activation of the tuberous sclerosis complex 2 (TSC2)/mammalian target of rapamycin (mTOR)/S6 pathway through the production of vascular endothelial growth factor (VEGF) in this carcinoma. ISL effectively prevented ACC-induced angiogenesis both in vitro and in vivo through inhibition of TSC2/mTOR/S6-mediated VEGF production. Inhibition of the TSC2/mTOR/S6 pathway by ISL was mediated through activation of c-Jun NH2-terminal kinase and inactivation of extracellular signal-regulated kinase and not through the classical phosphatidylinositol 3-kinase/Akt pathway. These results demonstrate that ISL effectively modulates ACC-induced angiogenesis through inhibition of TSC2/mTOR/S6 signaling and that sensitivity to ISL was correlated with mTOR activation status in these carcinomas.
See article at J Pharmacol Exp Ther 2010, 334:500–512.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics