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Cordycepin (3'-deoxyadenosine), a major bioactive compound of Cordycepsmilitaris, has many pharmacological actions, such as anti-inflammatory and anticanceractivities. In this study, the relationship between inhibition of cell motilityand anti-invasive activity by cordycepin in LNCaP human prostate carcinoma cellswas investigated. Within the concentration range that was not cytotoxic, cordycepintime-dependently inhibited cell motility and invasiveness of LNCaP cells. Theinhibitory effects of cordycepin on cell invasiveness were associated with tighteningof tight junctions (TJs), which was demonstrated by an increase in transepithelialelectrical resistance (TER). Immunoblotting indicated that cordycepin decreaseslevels of claudin proteins, which are major components of TJs that play a keyrole in control and selectivity of paracellular transport. Furthermore, cordycepininhibited the expression and activity of matrix metalloproteinase (MMP)-2 andMMP-9, and simultaneously increased levels of tissue inhibitor of metalloproteinase(TIMP)-1 and TIMP-2. These effects were related to inactivation of the phosphoinositide3-kinase (PI3K)/Akt pathway in LNCaP cells. These findings suggest that cordycepininhibits the migration and invasion of LNCaP cells by downregulating the activityof TJs and MMPs, possibly in association with suppression of Akt activation.

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