Figure 8.

Nimbolide exerts anti-tumor activity in a human WM xenograft model. Female SCID mice (n=20) were subcutaneously implanted with 1 × 10⁶ RPCI-WM1 cells (as described in the Supplementary methods). Progressive increase in IgM was measured in the serum and this corresponded with tumor growth in a time-dependent fashion. On average, WM tumor tissues grew to a median of 3 cm and IgM levels reached a median of 823 ng ml⁻¹ by Day 30 post-implantation. (a) Average tumor reduction in the nimbolide 100 mg kg⁻¹ cohort was 48% with no additional anti-WM benefit noted in the 200 mg kg⁻¹ cohort. (b) Tumors from two representative mice (control and nimbolide 100 mg kg⁻¹) show a significant reduction in nimbolide-treated mice (~50%). (c) Human IgM levels measured by ELISA were significantly lower in nimbolide treated mice vs control (DMSO). Data from 15 mice is shown as representatives of the 3 different treatment groups. *P<0.005. (d) IHC analysis of tumor samples taken from DMSO and nimbolide (100 mg kg⁻¹) treated mice shows changes in IgM, Ki-67 and BCL2. The TP53 protein did not appear changed. Cleaved caspase-3 (Casp-3) was notably increased in nimbolide-treated mice.