Identification of the alternative target for translation inhibitory antitumor drugs
December 10, 2020
Cancer cells with higher sensitivity to the drug can be predicted
An international collaborative research group including RIKEN Cluster for Pioneering Research and RIKEN CSRS has newly identified DDX3, a translation initiation factor, as a target protein for rocaglamide A, a plant-derived translation inhibitor with anti-cancer effects.
Rocaglamide A has been studied as an effective anti-cancer agent. It has been found that its binding to the target translation initiator "eIF4A" inhibits translation and suppresses the growth of cancer cells.
The group identified DDX3 in addition to eIF4A as the target protein of rocaglamide A by using an original fluorescence labeling method (NBD method). Understanding of the action mechanism revealed that, unlike regular translation inhibitors, the inhibitory effect of rocaglamide A on cell growth is higher in cancer cells with higher expression levels of DDX3 and eIF4A.
The results of this study are expected to contribute to prediction of cancer cells with higher effects of rocaglamide A.
Cell Chemical Biology doi:10.1016/j.chembiol.2020.11.008
M. Chen, M. Asanuma, M. Takahashi, Y. Shichino, M. Mito, K. Fujiwara, H. Saito, S. N. Floor, N. T. Ingolia, M. Sodeoka, K. Dodo, T. Ito, S. Iwasaki,
"Dual targeting of DDX3 and eIF4A by the translation inhibitor rocaglamide A".
Catalysis and Integrated Research Group