The cellular and molecular mechanisms of cordycepin induced apoptosis in MA-10 mouse Leydig tumor cells

Abstract

The incidence of testicular cancer between 1999 and 2008 in Taiwan from 0 85 increased to 1 54 per population of hundred thousand people and radical orchidectomy combined with chemotherapy is the common protocol to treat testicular and Leydig cell cancers However these drugs used for chemotherapy could cause drug toxicity side effects and serious impacts on the quality of life Thus people more focus on developing lower side effect chemotherapy drugs to improve prognosis in recent years Cordycepin also called 3’-deoxyadenosine has been identified as a major bioactive metabolite in Cordyceps sinensis It possesses a wide range of biological effects including stimulation on steroidogenesis anti-inflammatory effect inhibition of platelet aggregation and anti-cancer effect We have found that cordycepin could induce testicular tumor cell apoptosis The p38 MAPKs play important roles in the regulation of balance between cell survival and cell death on the development of various cancers However the roles of p38 MAPKs regulating apoptotic effects on Leydig tumor cells remain unclear In the present study we showed that cordycepin (3?-deoxyadenosine) selectively induced apoptosis in MA-10 mouse Leydig tumor cells through regulating the p38 MAPKs and PI3K/AKT signaling pathways Cordycepin reduced viability in MA-10 TM4 and NT2/D1 cells but not cause cell death of primary mouse Leydig cells on moderate concentration Cordycepin increased reactive oxygen species (ROS) levels which is associated with the induction of apoptosis as characterized by positive Annexin V binding activation of caspase-3 and cleavage of PARP Inhibition of p38 MAPKs activity by SB203580 significantly prevented cordycepin-induced apoptosis in MA-10 cells Co-treatment with wortmannin or the autophagy inhibitor 3-methyladenine (3-MA) elevated levels of apoptosis in cordycepin-treated MA-10 cells Moreover cordycepin activated p53 p21 and TGF?; and downregulated CDK2 The antitumour activity of cordycepin-treated MA-10 cells was significantly distinct in severe combined immunodeficiency (SCID) mice in vivo These results suggested that cordycein is a highly selective treatment to induce MA-10 cells apoptosis via p38 MAPKs signaling

Date of Award	2015 Nov 17
Original language	English
Supervisor	Bu-Miin Huang (Supervisor)