oroxylin-a-7-o-glucuronide and Neoplasm-Metastasis

Malignant glioma are linked to a high mortality rate. Therefore, it is necessary to explore and develop effective therapeutic strategy. Oroxyloside is a metabolite of oroxylin A. However, its inhibitory effects on cancer are little to be known. In the present study, we investigated the effects of oroxyloside on cell proliferation, migration, and apoptosis in vitro and in vivo in human glioma. The results indicated that oroxyloside significantly suppressed the proliferation of human glioma cells through inducing cell cycle arrest at G0/G1 phase through reducing Cyclin D1 and cyclin-dependent kinase 2 (CDK2) while enhancing p53 and p21 expressions. In addition, the migration of glioma cells was dramatically inhibited by oroxyloside in a dose-dependent manner, which was related to its modulation on extracellular matrix (ECM), as evidenced by up-regulated E-cadherin, and metastasis-associated protein 3 (MTA3), whereas down-regulated N-cadherin, Vimentin, Twist, alpha-smooth muscle actin (α-SMA) and Syndecan-2. Furthermore, oroxyloside treatment markedly induced apoptosis in glioma cells through improving Caspase-9, Caspase-3 and PARP cleavage, accompanied with high release of cytochrome c (Cyto-c) into cytoplasm and subsequently increase of apoptotic protease-activating factor 1 (Apaf-1). In vivo, oroxyloside administration significantly inhibited the glioma cell xenograft tumorigenesis through various signaling pathways, including suppression of Cyclin D1/CDK2 and ECM pathways, as well as potentiation of p53/p21 and Caspases pathways. Together, the findings above illustrated that oroxyloside, for the first time, was used as a promising candidate against human glioma.

Topics: Animals; Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cytochromes c; Disease Progression; Flavones; Glioma; Glucuronides; Humans; Male; Mice, Inbred BALB C; Mice, Nude; Neoplasm Metastasis; Signal Transduction; Xenograft Model Antitumor Assays