Molecular mechanisms and anti‐cancer aspects of the medicinal phytochemicals rocaglamides (=flavaglines)

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.