Cordycepin Inhibits Human Gestational Choriocarcinoma Cell Growth by Disrupting Centrosome Homeostasis.

Abstract

IntroductionHuman 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 MethodsHere, 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.ResultsHere, 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.ConclusionThus, our study demonstrates that cordycepin inhibits cell proliferation and disrupts the cytoskeleton by triggering centrosome amplification.