The Effect of Cordycepin on Steroidogenesis and Apoptosis in MA‐10Mouse Leydig Tumor Cells

Abstract

Cordycepin is a natural pure compound extracted from Cordyceps sinensis (CS). We have demonstrated that CS stimulates steroidogenesis in primary mouse Leydig cell and activates apoptosis in MA-10 mouse Leydig tumor cells. It is highly possible that cordycepin is the main component in CS modulating Leydig cell functions. Thus, our aim was to investigate the steroidogenic and apoptotic effects with potential mechanism of cordycepin on MA-10 mouse Leydig tumor cells. Results showed that cordycepin significantly stimulated progesterone production in dose- and time-dependent manners. Adenosine receptor (AR) subtype agonists were further used to treat MA-10 cells, showing that A1, A 2A , A 2B , and A3, AR agonists could stimulate progesterone production. However, StAR promoter activity and protein expression remained of no difference among all cordycepin treatments, suggesting that cordycepin might activate AR, but not stimulated StAR protein to regulate MA-10 cell steroidogenesis. Meanwhile, cordycepin could also induce apoptotic cell death in MA-10 cells. Moreover, four AR subtype agonists induced cell death in a dose-dependent manner, and four AR subtype antagonists could all rescue cell death under cordycepin treatment in MA-10 cells. In conclusion, cordycepin could activate adenosine subtype receptors and simultaneously induce steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells.

A Systematic Review of the Biological Effects of Cordycepin

“…A major outstanding issue that is hampering the development of cordycepin as a lead compound is the lack of a clearly identified cordycepin-binding target molecule and a mechanism of action that connects this binding with the therapeutic effects. Proposed binding targets include poly (A) polymerases, adenosine receptors, CDK2, PARP1, AKT, AMPK, FGFR2 and RuvB-like ATPase 2 (RUVBL2) [ 31 , 32 , 35 , 40 , 65 , 66 , 106 , 145 , 155 , 167 , 201 , 210 , 239 , 268 , 269 , 270 , 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 ]. A recent careful evaluation of AMPK as a cordycepin target concluded that although it is bound and activated by cordycepin monophosphate, AMPK activation is not responsible for the effects of cordycepin on cell survival [ 166 ].…”

The Chemical Constituents and Pharmacological Actions ofCordyceps sinensis

“…Qian et al considered that cordycepin is a potent anti-inflammatory and analgesic medicine. There are several studies demonstrating that C. sinensis stimulates steroidogenesis in primary mouse Leydig cell and activates apoptosis in MA-10 mouse Leydig tumor cells in dose- and time-dependent manners [ 27 , 28 ]. The steroidogenic and apoptotic mechanism of cordycepin is also clear—cordycepin stimulated intracellular PLC/PKC and MAPK signal transduction pathways to induce steroidogenesis and cell death in MA-10 mouse Leydig tumor cells [ 29 ].…”

Transcriptomic Responses of Cordyceps militaris to Salt Treatment During Cordycepins Production

“…Afterward, the cAMP formation was inhibited, then the serine/threonine kinase glycogen synthase kinase (GSK)-3β/β-catenin signaling pathway and subsequently cell division were indirectly inactivated and suppressed, respectively ( 15 ). Additionally, it has been also documented that cordycepin effects on inhibiting platelet aggregation, inducing steroid formation, and with broad-spectrum antibiotic activity by inhibiting NAD + -dependent DNA ligase ( 13 , 16 , 17 ).…”