Drug Design, Development and Therapy (Jul 2020)
Cordycepin Inhibits Human Gestational Choriocarcinoma Cell Growth by Disrupting Centrosome Homeostasis
Abstract
Chia-Yih Wang,1,2,* Shih-Wei Tsai,3,* Han-Hsiang Chien,1 Ting-Yu Chen,2,4 Shi-Yuan Sheu,5,6 Edmund Cheung So,7,8 Bu-Miin Huang1,9 1Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Obstetrics and Gynecology, An Nan Hospital, China Medical University, Tainan, Taiwan; 4Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; 5School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan; 6Department of Chinese Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan; 7Department of Anesthesia & Medical Research, An Nan Hospital, China Medical University, Tainan, Taiwan; 8Graduate Institute of Medical Sciences, Chang Jung Christian University Tainan, Tainan, Taiwan; 9Institute of Medical Research, China Medical University, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Edmund Cheung So; Bu-Miin Huang Tel +886-6-3553111 ext.1517; +886-6-2353535 ext. 5337Fax +886-6-3553111; +886-6-2093007Email [email protected]; [email protected]: Human gestational choriocarcinoma, a type of gestational trophoblastic disease, occurs after miscarriage, abortion, ectopic pregnancy, or molar pregnancy. Despite recent advances in the mechanism of anticancer drugs that induce human gestational choriocarcinoma apoptosis or block its growth, new therapeutic approaches are needed to be established. Cordycepin is an active anti-cancer component extracted from Cordyceps sinensis. It prevents cell proliferation both in vitro and in vivo.Materials and Methods: Here, we examined cell growth by counting cell numbers, and performing a flow cytometry assay and EdU incorporation assay. Centrosome and cytoskeleton-related structures were observed by immunofluorescence assay. The DNA damage-related signaling was examined by Western blot assay.Results: Here, we showed that cordycepin inhibited human gestational choriocarcinoma cell proliferation and induced cell death. In addition, treatment with cordycepin activated DNA-PK and ERK, thus inducing centrosome amplification and aberrant mitosis. These amplified centrosomes also disrupted microtubule arrays and actin networks, thus leading to defective cell adhesion. Furthermore, cordycepin induced autophagy for triggering cell death.Conclusion: Thus, our study demonstrates that cordycepin inhibits cell proliferation and disrupts the cytoskeleton by triggering centrosome amplification.Keywords: human gestational choriocarcinoma, cordycepin, centrosome, cell growth, microtubule
