Inhibition of migration and invasion of LNCaP human prostate carcinoma cells by cordycepin through inactivation of Akt

Abstract

Abstract. Cordycepin (3'-deoxyadenosine), a major bioactive compound of Cordyceps militaris, has many pharmacological actions, such as anti-inflammatory and anticancer activities. In this study, the relationship between inhibition of cell motility and anti-invasive activity by cordycepin in LNCaP human prostate carcinoma cells was investigated. Within the concentration range that was not cytotoxic, cordycepin time-dependently inhibited cell motility and invasiveness of LNCaP cells. The inhibitory effects of cordycepin on cell invasiveness were associated with tightening of tight junctions (TJs), which was demonstrated by an increase in transepithelial electrical resistance (TER). Immunoblotting indicated that cordycepin decreases levels of claudin proteins, which are major components of TJs that play a key role in control and selectivity of paracellular transport. Furthermore, cordycepin inhibited the expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9, and simultaneously increased levels of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. These effects were related to inactivation of the phosphoinositide 3-kinase (PI3K)/Akt pathway in LNCaP cells. These findings suggest that cordycepin inhibits the migration and invasion of LNCaP cells by downregulating the activity of TJs and MMPs, possibly in association with suppression of Akt activation.

Flavonoids from Orostachys japonicus A. Berger Inhibit the Invasion of LnCaP Prostate Carcinoma Cells by Inactivating Akt and Modulating Tight Junctions

“…However, FEOJ also inhibited MMP-2 and MMP-9 expression at the transcriptional level. That means the down-regulation of MMP-2 and MMP-9 expression did not resulted from FEOJ-induced up-regulation of TIMP-1 and TIMP-2 expression itself even though there is a report that the agent that have an inhibitory effect on PI3K/Akt pathway show the exactly same results [27]. Therefore, we need to further detailed experiment by silencing each gene to elucidate the mechanisms.…”

Effect of AKT inhibition on epithelial-mesenchymal transition and ZEB1-potentiated radiotherapy in nasopharyngeal carcinoma

“…AKT has previously been hypothesized to function as a positive and negative effector of mammary tumorigenesis, a tumor suppressor at early stages and a stimulator of tumor invasion at later stages (26). In addition, the phosphorylation of AKT has been demonstrated to correlate with a poor prognosis in a number of types of human cancer (27).…”

Resistance to the mTOR-inhibitor RAD001 elevates integrin α2- and β1-triggered motility, migration and invasion of prostate cancer cells

“…Concerning metastatic progression, activation of the Akt pathway has been shown to correlate with the chemotactic motility of prostate cancer cells in vitro (Jeong et al , 2012) and prostate tumour progression to metastasis in the transgenic adenocarcinoma mouse prostate mouse model (Sakamoto et al , 2010). Indeed, Akt blockade strongly diminished chemotaxis of PC3 par cells, which corroborates both reports.…”