Anticancer Effects of Cordyceps Militaris Extract in Human Ovarian Cancer Cells via ADORA2B (P05-012-19)

Abstract

ObjectivesThe study was aimed to determine anticancer effects of Cordyceps militaris extract (CME) and its major bioactive compound, cordycepin, in human ovarian cancer cells, and to identify their putative molecular mechanism mediated by adenosine receptors (ADORAs). MethodsCME was prepared in 50% ethanol solution. LC-MS was used for quantification and Q-TOF MS for qualifying bioactive compounds in CME. MTT assay was performed for cell viability in A2780, SKOV-3, TOV112D, and OVCAR-3 human ovarian cancer cell lines. cAMP response element (CRE)-luciferase reporter gene assays were used to determine whether antitumorigenic effect of CME/cordycepin is based on adenosine derivatives. Additionally, the involvement of ADORA signaling pathway was measured using with ADORA2A antagonist SCH 58261 and ADORA2B antagonist PSB 603. ResultsCordycepin concentrations of CME was 21.8%. CME was effective to reduce cell viability in A2780 and OVCAR-3 with IC50 115.2 μg/ml and 155.94 μg/ml respectively, while SKOV-3 and TOV112D were relatively resistant to CME. cAMP production was significantly increased by treatment with cordycepin and, lesser extent, with CME. Among the four types of ADORAs, ADORA2A and 2B showed relatively higher expression levels in ovarian cancer cells. The cAMP production by CME was ameliorated by PSB 603, not SCH 58261, treatment. ConclusionsCME and cordycepin have anticancer effects in human ovarian cancer cells via ADORA2B-cAMP pathway. Funding SourcesNRF of Korea (2017R1D1A1B03034936 & 22A20130012143) and Health Fellowship Foundation.