Cordycepin generally inhibits growth factor signal transduction in a systems pharmacology study

Lawrence, Steven; Lin, Jialiang; Khurshid, Asma; Utami, Wahyu; Singhania, Richa; Ashraf, Sadaf; Thorn, Graeme J.; Mangangcha, Irengbam Rocky; Spriggs, Keith; Kim, Dong‐Hyun; Barrett, David; de Moor, Cornelia H.

doi:10.1002/1873-3468.15046

Cordycepin generally inhibits growth factor signal transduction in a systems pharmacology study

Lawrence, Steven; Lin, Jialiang; Khurshid, Asma; Utami, Wahyu; Singhania, Richa; Ashraf, Sadaf; Thorn, Graeme J.; Mangangcha, Irengbam Rocky; Spriggs, Keith; Kim, Dong‐Hyun; Barrett, David; de Moor, Cornelia H.

Authors

Steven Lawrence

Jialiang Lin

Asma Khurshid

Wahyu Utami

Richa Singhania

Sadaf Ashraf

Graeme J. Thorn

Irengbam Rocky Mangangcha

Dr KEITH SPRIGGS KEITH.SPRIGGS@NOTTINGHAM.AC.UK
ASSOCIATE PROFESSOR

Dr DONG-HYUN KIM Dong-hyun.Kim@nottingham.ac.uk
ASSOCIATE PROFESSOR

David Barrett

Dr CORNELIA DE MOOR CORNELIA.DE_MOOR@NOTTINGHAM.AC.UK
ASSOCIATE PROFESSOR

Abstract

Cordycepin (3′ deoxyadenosine) has been widely researched as a potential cancer therapy, but many diverse mechanisms of action have been proposed. Here, we confirm that cordycepin triphosphate is likely to be the active metabolite of cordycepin and that it consistently represses growth factor-induced gene expression. Bioinformatic analysis, quantitative PCR and western blotting confirmed that cordycepin blocks the PI3K/AKT/mTOR and/or MEK/ERK pathways in six cell lines and that AMPK activation is not required. The effects of cordycepin on translation through mTOR pathway repression were detectable within 30 min, indicating a rapid process. These data therefore indicate that cordycepin has a universal mechanism of action, acting as cordycepin triphosphate on an as yet unknown target molecule involved in growth factor signalling.

Citation

Lawrence, S., Lin, J., Khurshid, A., Utami, W., Singhania, R., Ashraf, S., Thorn, G. J., Mangangcha, I. R., Spriggs, K., Kim, D., Barrett, D., & de Moor, C. H. (2025). Cordycepin generally inhibits growth factor signal transduction in a systems pharmacology study. FEBS Letters, 599(3), 415-435. https://doi.org/10.1002/1873-3468.15046

Journal Article Type	Article
Acceptance Date	Oct 2, 2024
Online Publication Date	Nov 7, 2024
Publication Date	2025-02
Deposit Date	Dec 19, 2024
Publicly Available Date	Dec 19, 2024
Journal	FEBS Letters
Print ISSN	0014-5793
Electronic ISSN	1873-3468
Publisher	Wiley
Peer Reviewed	Peer Reviewed
Volume	599
Issue	3
Pages	415-435
DOI	https://doi.org/10.1002/1873-3468.15046
Public URL	https://nottingham-repository.worktribe.com/output/41678103
Publisher URL	https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.15046