Cordycepin inhibits ERK pathway to suppress FGF9-induced tumorigenesis with MA-10 mouse Leydig tumor cells

Li Ching Chen, Chin Ying Chen, Yi-Ping Lee, Bu Miin Huang

Research output: Contribution to journalArticlepeer-review

Abstract

Fibroblast growth factor 9 (FGF9) is a member of FGF family, and abnormal expression of FGF9 can promote tumorigenesis. Cordycepin, a major bioactive component in fungus Cordyceps sinensis, could suppress various tumors. We have shown that cordycepin could inhibit FGF9-induced testicular tumor growth in vitro and in vivo with MA-10 mouse Leydig tumor cells. In the present study, the mechanisms related to apoptosis and autophagy were determined. Results show that cordycepin significantly suppressed cell viability and colony formation with correlatedly morphological change related to cell death in FGF9-treated MA-10 cells. Flow cytometry and western blotting results further demonstrate that cordycepin induced apoptosis through the cleavage of caspase-8,-9,-3 and PARP in FGF9-treated MA10 cells. However, the expressions of LC3-II, beclin-1 and p62 were not stimulated by cordycepin with the presence of FGF9, suggesting cordycepin would activate apoptosis, but not autophagy, in FGF9-treated MA-10 cells. Moreover, inhibition of ERK signal pathway and autophagy would enhance cordycepin-induced cell death effects in FGF9-treated MA-10 cells, referring that ERK signaling was regulated under cordycepin and FGF9 treatments. In NOD-SCID mouse allograft model inoculated with MA-10 cells, cordycepin significantly suppressed tumor growth with the presence of FGF9, and the cleavage of caspase-3 could be observed in tumor tissue, implying cordycepin induced caspase cascade to suppress tumor growth. Moreover, cordycepin plus U0126, ERK inhibitor, further significantly suppressed tumor growth with the presence of FGF9 as compared to the FGF9 only group, confirming the involvement of ERK signaling in this event. In conclusion, cordycepin induced caspase and ERK pathways to promote MA-10 cell apoptosis, but not autophagy, with the presence of FGF9.

Original languageEnglish
Article number8
Pages (from-to)485-501
Number of pages17
JournalJournal of Food and Drug Analysis
Volume31
Issue number3
DOIs
Publication statusPublished - 2023

All Science Journal Classification (ASJC) codes

  • Food Science
  • Pharmacology

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