Anticancer and antimetastatic effects of cordycepin, an active component of Cordyceps sinensis

Abstract

Cordyceps sinensis, a fungus that parasitizes on the larva of Lepidoptera, has been used as a valued traditional Chinese medicine. We investigated the effects of water extracts of Cordyceps sinensis (WECS), and particularly focused on its anticancer and antimetastatic actions. Based on in vitro studies, we report that WECS showed an anticancer action, and this action was antagonized by an adenosine A3 receptor antagonist. Moreover, this anticancer action of WECS was promoted by an adenosine deaminase inhibitor. These results suggest that one of the components of WECS with an anticancer action might be an adenosine or its derivatives. Therefore, we focused on cordycepin (3'-deoxyadenosine) as one of the active ingredients of WECS. According to our experiments, cordycepin showed an anticancer effect through the stimulation of adenosine A3 receptor, followed by glycogen synthase kinase (GSK)-3β activation and cyclin D1 suppression. Cordycepin also showed an antimetastatic action through inhibiting platelet aggregation induced by cancer cells and suppressing the invasiveness of cancer cells via inhibiting the activity of matrix metalloproteinase (MMP)-2 and MMP-9, and accelerating the secretion of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 from cancer cells. In conclusion, cordycepin, an active component of WECS, might be a candidate anticancer and antimetastatic agent.

Toxicity evaluation of cordycepin and its delivery system for sustained in vitro anti-lung cancer activity

“…It showed that some cells were damaged at the epithelia resulting in the release of the cytoplasm. Our data also confirmed the in vitro cytotoxic effect of cordycepin toward cancer cells, corresponding to that reported elsewhere [26][27][28].…”

Cordycepin inhibits chondrocyte hypertrophy of mesenchymal stem cells through PI3K/Bapx1 and Notch signaling pathway

“…Cordycepin, a nucleoside adenosine, is an effective substance of cordyceps (9). It has been reported that cordycepin possesses various biological functions, including antioxidant, hypolipidemic, and anti-inflammatory activities (10, 11).…”

<b>Cordycepin induces apoptotic cell death and inhibits cell migration in renal cell carcinoma via regulation of microRNA-21 and PTEN </b><b>phosphatase </b>

“…Traditional Chinese medicine is one of them for complementary and alternative therapy. Cordycepin, an active compound extracted from one Traditional Chinese medical herb, Cordyceps militaris, has been studied to treat many cancers including lung cancer (50), ovarian cancer (46), leukemia (30), breast cancer (47), brain cancer (19), colon cancer (27), liver cancer (25), and so on (33). Recently, some efforts have been done to investigate the po- PTEN/PI3K/Akt signaling pathway is an important pathway regulated by microRNA-21 (7).…”

“…Development of neo-adjuvant therapy is still in a demand at present. Cordycepin is a main active composition extracted from Cordyceps militaris and has been reported to harbor anti-tumor activity in a broad spectrum of cancer types, including lung cancer (50), ovarian cancer (46), leukemia (30), breast cancer (47), and so on (33). Two recent reports firstly demonstrated that cordycepin could induce apoptosis in renal cell carcinoma through Erk-JNK signaling pathway (20,48) and indicated the potential application of cordycepin in treating renal cell carcinoma.…”