Ribosome Inactivating Proteins: Exploiting Plant Weapons to Fight Human Cancer

Abstract

Ribosomeinactivating proteins (RIPs) are potent toxins from plant or bacterial origin that work by irreversibly block ribosomes of target cells, causing apoptotic cell death. Their noteworthy activity has been exploited to therapeutic purpose in the treatment of cancer. The specificity for malignant cells has been addressed by using targeting domains such as antibodies to form immunotoxins or ligands to get chimeric fusions. These therapeutics have shown encouraging preliminary results in hematological tumors as well as in solid tumors with the most effective ones currently undergoing clinical trials. Denileukin diftitox, a fusion between the catalytic domain of the diphtheria toxin and human cytokine interleukin-2, was the first toxin-derived drug approved by the FDA. Another, more recent way to take advantage of RIPs is to utilize their DNA in the suicide gene therapy. Toxin DNA can be delivered trough a vector to or complexed and directly injected in the tumor. In the future RIPs are expected in to give a significant contribution in the treatment of the cancer, also in combination with traditional therapies. The scope of this review is to highlight advantages and drawbacks of RIP based biomedical applications, by evaluating their employment as either targeted proteins or genes as effectors.