Figure 6.

Curcumin suppresses the development of leukemic cells (CD19⁺/CD5⁺) and reduces NOTCH1 signaling in Eμ-TCL1 mice. (A) qPCR analysis of ATF4 and CHOP in B cells from the spleen or BM from C57BL/6 WT (N = 6) or Eμ-TCL1 mice (N = 6). (B) qPCR analysis of HES1 and DTX1 mRNA levels in B cells from the spleen or BM of C57BL/6 or Eμ-TCL1 mice. (C) Western blot analysis and bar graph of NICD. (D) Eight-month-old Eμ-TCL1 mice were injected intraperitoneally with curcumin (50 mg/kg/day) dissolved in a vehicle (corn oil) or with vehicle alone daily for 2 months and evaluated according to the scheme depicted (upper panel). The expansion of CD19⁺/CD5⁺ cells in the PB (N = 4 per group) was assessed by flow cytometry at the indicated time points (bottom panel). (E) Accumulation of CD19⁺/CD5⁺ cells in the spleen, liver, and BM of Eμ-TCL1 mice treated with curcumin or vehicle (N = 4, per group) assessed by flow cytometry. (F) Western blot analysis of CD19⁺/CD5⁺-sorted cells of BM, indicating the significant reduction of NICD expression (N = 4, per group) and a tendency of reduction for HES1 (N = 3, per group). Data are presented as mean ± SD. (A-F) *P< 0.05, **P< 0.01; ns, not significant as determined by unpaired t-test. (G) Kaplan–Meier survival plot of Eμ-TCL1 mice treated with curcumin (N = 8) or vehicle alone (N = 8) from two independent experiments. Overall survival was determined by using Kaplan–Meier curves and log-rank (Mantel–Cox) test.