Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 137, Issue 8, Pages 1791-1799Publisher
WILEY
DOI: 10.1002/ijc.29013
Keywords
anticancer therapy; Rocaglamide; Flavagline
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Rocaglamides (= flavaglines) are potent natural anti-cancer phytochemicals that inhibit cancer growth at nanomolar concentrations by the following mechanisms: (1) inhibition of translation initiation via inhibition of phosphorylation of the mRNA cap-binding eukaryotic translation initiation factor eIF4E and stabilization of RNA-binding of the translation initiation factor eIF4A in the eIF4F complex; (2) blocking cell cycle progression by activation of the ATM/ATR-Chk1/Chk2 checkpoint pathway; (3) inactivation of the heat shock factor 1 (HSF1) leading to up-regulation of thioredoxin-interacting protein (TXNIP) and consequent reduction of glucose uptake and (4) induction of apoptosis through activation of the MAPK p38 and JNK and inhibition of the Ras-CRaf-MEK-ERK signaling pathway. Besides the anti-cancer activities, rocaglamides are also shown to protect primary cells from chemotherapy-induced cell death and alleviate inflammation- and drug-induced injury in neuronal tissues. This review will focus on the recently discovered molecular mechanisms of the actions of rocaglamides and highlights the benefits of using rocaglamides in cancer treatment.
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