Cordycepin and a preparation from Cordyceps militaris inhibit malignant transformation and proliferation by decreasing EGFR and IL-17RA signaling in a murine oral cancer model
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Peng-Yang Hsu1, Yueh-Hsin Lin2, Erh-Ling Yeh1, Hui-Chen Lo3, Tai-Hao Hsu1 and Che-Chun Su1,4,5,6
1Department of Bioindustry Technology, Da-Yeh University, Datsuen, Taiwan
2Department of Nutrition and Dietetics, Changhua Christian Hospital, Taiwan
3Department of Nutritional Science, Fu Jen Catholic University, Taiwan
4Graduate Institute of Statistics and Information Science, National Changhua University of Education, Taiwan
5Department of Internal Medicine, Changhua Christian Hospital, Taiwan
6Laboratory of Immunology, Changhua Christian Hospital, Taiwan
Che-Chun Su, email: firstname.lastname@example.org
Tai-Hao Hsu, email: email@example.com
Keywords: Cordyceps militaris, cordycepin, oral cancer, EGFR, IL-17A tumoricidal activity
Received: August 13, 2017 Accepted: September 20, 2017 Published: October 04, 2017
Cordyceps militaris (CM) and its active ingredient cordycepin have been reported to inhibit tumor growth, but the mechanisms are not fully understood. This study used a mouse model for oral cancer and a cell line, 4NAOC-1 derived from the model to study the mechanisms. Our results show that a CM preparation (CMP) can significantly inhibit tumor development and malignant transformation in the model. In vitro data indicate that CMP and cordycepin can inhibit 4NAOC-1 cell proliferation, either anchorage-dependent or -independent. Cordycepin can also increase cell apoptosis, and decrease cell mitosis and EGFR signaling. In accordance, CMP treatment can significantly decrease the levels of ki-67 and EGFR signaling molecules in cancer tissues. We also found that the levels of IL-17A in cancer tissues of control mice were significantly increased, and CMP inhibited these levels. IL-17A can stimulate cancer cell proliferation, which can be suppressed by cordycepin. Furthermore, cordycepin can reduce the expression of IL-17RA and its downstream signaling molecules. Moreover, CMP and cordycepin can significantly decrease IL-17A production in vitro and in vivo. Finally, CMP and its ingredients can enhance tumoricidal activities with increase in IFN-γ and TNFα, and decrease PD-L1 expression. In conclusion, CMP and its ingredient cordycepin can inhibit tumor growth and malignant transformation in a mouse model for oral cancer via inhibition of EGFR- and IL-17RA-signaling and enhancement of anti-tumor immunity.
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