AD 198 exhibited potent anti-proliferative/survival-inhibitory effects on TRAF3
mouse B lymphoma and human MM cells. Tumor B cells were treated with various concentrations of AD 198 for 24 h. Total viable cell numbers were subsequently determined by MTT assay. (A and B) Effects on primary splenic B lymphoma cells harvested from diseased B-TRAF3-/- mice. Panel A shows the activity of AD 198 examined with a wide range of doses (1:10 serial dilutions). Panel B shows refined dose-dependent effects of AD 198 (examined at 1:2 serial dilutions). Similar results were also obtained with primary B lymphoma cells purified from ascites, cervical and mesenteric LNs of several individual B-TRAF3-/- mice with spontaneous tumors. (C) Effects on TRAF3-/- B lymphoma cell lines derived from 3 individual B-TRAF3-/- mice, including 105–8.1B6 (105–8), 115–6.1.2 (115–6), and 27–9.5.3 (27–9). (D) Effects on human patient-derived MM cell lines with TRAF3 bi-allelic deletions or frameshift mutations, including 8226, KMS11 and LP1. The graphs depict the results of three independent experiments with duplicate samples in each experiment (mean ± SEM).