Cyproheptadine inhibits growth of leukemia and myeloma cells in mouse models. MDAY-D2 cells (5 × 105) were injected intraperitoneally into DBA2 mice. Mice were then treated with cyproheptadine (CYP; 40 mg/kg per day; n = 10) or vehicle control (n = 10) intraperitoneally for 1 week. At the end of treatment, the mice were killed. (A) The volume of malignant ascites in the peritoneal cavity was measured. (B) The total number of malignant MDAY-D2 cells in the malignant ascites was counted. The bar represents the median of the population. (C) LP-1 myeloma cells (10 × 106) were injected subcutaneously into the flank of sublethally irradiated NOD/SCID mice. Two weeks after injection, mice were treated with cyproheptadine 36 mg/kg (n = 10) or vehicle control (n = 10) as described in “Assessment of cyproheptadine's antileukemic and antimyeloma activity in vivo.” Tumor volume was measured weekly with a caliper. Data represent the mean plus or minus SEM. *P = .048, **P = .032, by the Student t test. (D) LP-1 myeloma cells (10 × 106) were injected subcutaneously into the flank of sublethally irradiated NOD/SCID mice. When tumors were palpable, mice were treated intraperitoneally with cyproheptadine (10 mg/kg per day) or vehicle control. Ten days after treatment, mice were killed and the tumor was excised. From the excised tumors, cell lysates were prepared, normalized for total protein, and analyzed by SDS-PAGE/immunoblotting using antibodies specific for cyclin D2 (CCND2) and anti–β-actin. Numbers represent tumors from individual mice. (E) MDAY-D2 murine leukemia cells (5 × 105) were injected subcutaneously into the flank of sublethally irradiated NOD/SCID mice. When tumors were palpable, mice were treated intraperitoneally with cyproheptadine (10 mg/kg per day) or vehicle control. Five days after treatment, mice were killed and the tumor was excised. From the excised tumors, cell lysates were prepared, normalized for total protein, and analyzed by SDS-PAGE/immunoblotting using antibodies specific for cyclin D2 (CCND2), cyclin D3 (CCND3), and anti–β-actin. Numbers represent tumors from individual mice.
