The Cellular and Molecular Effects of Cordycepin on Cancer
Date Issued
2010
Date
2010
Author(s)
Yao, Wen-Ling
Abstract
Cordycepin (3’-deoxyadenosine), a well known bioactive compound extracted from a traditional Chinese medicine with complex of fungus (Cordyceps spp.) and infected caterpillar-grown, has been reported to contribute to the anti-tumor, insecticidal and anti-bacterial activity. However, the cellular and molecular effect of cordycepin to cause anti-cancer action has never been elucidated. In this study, we test the anti-migratory/invasive, anti-proliferative and anti-survival effects and evaluate the molecular targets
of cordycepin in human hepatocellular carcinoma (HCC) and human leukemia cells. We found that cordycepin significantly suppressed cell proliferation of SK-Hep-1 (a HCC cell line) and U937 (a human leukemic monocyte lymphoma) cells. Cordycepin inhibits cell migration/invasion which is correlated with decreased expression of adhesive molecules, integrin β1 and α6 with a concentration dependent manner in SK-Hep-1 cells. Furthermore, a hallmark suppressor of cancer cell epithelial-mesenchymal transition (EMT) and migration/invasion, E-cadherin, was increased by treatment of cordycepin in SK-Hep1 cells. In U937 leukemia cells, the expression of β-catenin and its downstream cell cycle regulator, cyclin D1 were decreased upon cordycepin treatment. Cordycepin reduces nuclear translocation of β-catenin and its stability through a proteasome-dependent protein degradation mechanism. Degradation of β-catenin can be restored by inhibitor of glycogen synthase kinase 3 (GSK-3) suggests the GSK-3/β-catenin plays an important role on cordycepin suppressed leukemia cell
proliferation. Furthermore, cordycepin represses the level of phosphorylated Akt which is well known to be the upstream signal regulator to control GSK-3 activity. Thus, cordycepin inhibits leukemia cell growth possibly via the PI3-K/Akt/GSK-3/β-catenin signal pathway. Moreover, it has been well characterized that a transcriptional factor, Wilms Tumor 1 (WT1) plays as an essential factor to regulate leukemia cell proliferation. We have observed that cordycepin inhibits the WT1 translocation and activation. Taken together, these results suggest that cordycepin suppresses HCC and leukemia cancer progression by distinct mechanisms. Cordycepin reduces HCC migration/invasion by affecting expression of cell adhesion molecules but inhibits leukemia cell proliferation by tightly controlling signal pathway and transcriptional regulators. In conclusion, our study reveals that cordycepin may serve as a potential small molecular agent for therapeutic strategy to suppress tumor growth and metastasis.
Subjects
cordycepin
hepatocellular carcinoma
leukemia
cell migration/adhesion
cell proliferation
integrins
beta-catenin
glycogen synthesis kinase 3
SDGs
Type
thesis
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