sinensis are too rare to obtain and very expensive. In addition, the content of each component of natural products is variable and it might be difficult to check their quality. Therefore, we chose the cultured fruiting body of C. sinensis produced by Xinhui Xinhan Artificial Cordyceps Factory (Guangdong, China) and supplied by Gunsei Co., Ltd. (Tokyo, Japan)

as our experimental material, and investigated the pharmacological effects of hot water extracts (70 °C for 5 min) of C. sinensis (WECS). We investigated the action of WECS on cancer, particularly on metastasis. As active ingredients of WECS, we focused on cordycepin (3′-deoxyadenosine) and examined its anticancer and antimetastatic effects and the mechanisms of these effects. It has been reported that cordycepin interacts in biochemical processes, including BIBW2992 purchase nucleic acid synthesis, platelet aggregation, metastasis, inflammatory reactions, apoptosis, and cell cycle signaling (3). In this review, we mainly present our research findings on cordycepin, as an active ingredient of WECS. In in vitro studies, Nakamura et al. investigated the anticancer effect of WECS against B16 mouse melanoma (B16) and Lewis lung carcinoma (LLC) cells, and WECS showed direct cytotoxicity against both B16

and LLC cells at 10 and 30 μg/mL (4). Nakamura R428 et al. indicated that WECS (100 μg/mL) induced the apoptosis of B16-F10 mouse melanoma cells after 48-h exposure in vitro, as determined by both the TdT-mediated dUTP-biotin nick end labeling

(TUNEL) method and the detection of a DNA ladder (5). Lee et al. also demonstrated that cordycepin induced apoptosis in human prostate PC-3 cells through a mitochondria-mediated, caspase-dependent pathway (6). Yoshikawa et al. reported that WECS (10 μg/mL) markedly inhibited the growth of B16-BL6 mouse melanoma (B16-BL6) cells, LLC cells, HT1080 human fibrosarcoma (HT1080) cells, and CW-2 human colon carcinoma (CW-2) cells, and the inhibitory effect of WECS was significantly antagonized by 1 μM 3-ethyl 5-benzyl 2-methyl-6-phenyl-4-phenylethynyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate ADP ribosylation factor (MRS1191), a selective adenosine A3 receptor antagonist. Furthermore, WECS included 2.34% w/w cordycepin and 0.12% w/w adenosine as components according to the HPLC-electrochemical detection (ECD) system (7). That is, one of the active ingredients of WECS inhibited the proliferation of four cancer cell lines by the stimulation of adenosine A3 receptors, and this active ingredient may be cordycepin and not adenosine. In in vitro studies, Nakamura et al. demonstrated that cordycepin showed marked inhibitory effects on the growth curves of B16-BL6 cells (IC50 = 39 μM) and LLC cells (IC50 = 48 μM), while adenosine and 2′-deoxyadenosine (up to 100 μM) had no effect on the growth of the two cancer cell lines.