Correlation of abrin‐mediated inhibition of protein synthesis and apoptosis

Abstract

The plant toxin, abrin, a type‐II ribosome inactivating protein, is extremely lethal, the human fatal dose being ~1 μg/kg body weight. Abrin has been classified as an agent for bioterrorism, which is of concern. Conversely, the high toxic property of abrin has been employed in generating immunotoxins, whereas its toxin moiety is conjugated to cell surface marker‐specific antibodies for cell‐targeted killing. Different cell types exhibit variable levels of sensitivity to abrin toxicity; therefore, adequate knowledge of the molecular mechanism that governs the activity of the protein would be a safeguard. To gain insights into this, two cell lines requiring strikingly different concentrations of abrin for inactivating ribosomes were studied. Employing conjugates of the wild‐type and active site mutant of abrin A chain with the ricin B chain, it was found that abrin‐induced apoptosis was dependent on inhibition of protein synthesis (PSI) leading to ER‐stress in Ovcar‐3 cells, but not in KB cells. Abrin was also observed to cause direct DNA damage in KB cells, while in Ovcar‐3 cells abrin‐induced DNA damage was found to be dependent on caspases. Overall, the study demonstrates that the correlation of abrin‐mediated PSI and apoptosis is cell‐specific and abrin can induce more than one pathway to cause cell death. © 2018 IUBMB Life, 71(3):357–363, 2019

Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic Signaling

“…It appears that both the intrinsic and the extrinsic pathway are involved in stenodactylin-induced cell death, reinforcing the idea that RIPs induce a complex response in intoxicated cells triggering multiple death pathways (Polito et al, 2009;Pervaiz et al, 2016). Furthermore, it has been recently reported that abrin, another type 2 RIP, can trigger cell death through many mechanisms in different cell lines (Tiwari and Karande, 2019). Stenodactylin treatment induces the disruption of mitochondrial membrane potential, as confirmed by JC-1 positive staining at 24 h. RIP-triggered mitochondria-associated apoptotic signaling was also previously described (Narayanan et al, 2005;Sikriwal et al, 2008;Bora et al, 2010;Polito et al, 2016c).…”

Heterophyllin: A New Adenia Toxic Lectin with Peculiar Biological Properties

“…This represents a fundamental requirement in anti-cancer therapy, since the use of drugs, able to trigger multiple death pathways, can avoid the selection of resistant clones. Further studies will be necessary to identify the involvement of autophagy and/or endoplasmic reticulum stress, which have been already described for some RIPs [ 16 , 47 , 48 , 49 , 50 , 51 , 52 ].…”