Multiple signal transduction pathways are involved in G₂/M growth arrest and apoptosis induced by the immunomodulator AS101 in multiple myeloma

Diphenyl Ditelluride: Redox-Modulating and Antiproliferative Properties

“…The aforementioned effects of DPDT, including cytotoxic effects and cell cycle arrest in the S- and G2/M phases, are consistent with those of other TopoI inhibitors (Scheme 2) [63]. The organotellurate immunomodulator AS101 induces G2/M arrest in myeloma cells and downregulates Cdc25C, Plk-1 (a serine/threonine kinase), and Ilk-1 (essential for regulating the activity of Akt) in mouse 5T33 myeloma cells [64, 65]. Halpert et al demonstrated that AS101 targets several proteins and pathways in mice, such as pAkt, Bax, and Bcl-2 [66].…”

Diphenyl Ditelluride‐Induced Cell Cycle Arrest and Apoptosis: A Relation with Topoisomerase I Inhibition

“…Interestingly, it was found that the OT compound AS101 reduced tumour growth in a dose-dependent manner by inducing drag of the cell cycle in T cells in G2/M phase, and inducing apoptosis at the highest concentrations activating the caspases 3 and 9 [29]. Moreover, it was described that the compound AS101 may be involved in G2/ M growth arrest and induced apoptosis in multiple myeloma [30]. Consistently, DPDT treatment induced a time-dependent increase in the number of apoptotic cells from the S and G2/ M portions of the cell cycle in HL-60 cells [3].…”

The tellurium-based immunomodulator, AS101 ameliorates adjuvant-induced arthritis in rats

“…The important role of the integrin α4β1 in RA is further highlighted in a study conducted by Raychaudhuri and colleagues, demonstrating the role of VLA-4 antagonism in the prevention of inflammation and matrix metalloproteinase (MMP) production in a murine model of accelerated collageninduced arthritis [32]. AS101 and the second-generation tellurium-based compound, SAS, exhibit an inhibitory role on the activity of several MMPs, such as MMP-2 and MMP-9, in vitro [33,34]. We believe that the anti-arthritic and anti-inflammatory driven response by AS101 depends, at least in part, upon its ability to interact with VLA-4, thereby abrogating the infiltration of inflammatory/ autoreactive VLA-4 + immune cells into the joints.…”