Casein induces the proliferation of bone marrow mononuclear cells, apoptosis of WEHI-3 leukaemic cells and increased survival in a leukaemia mouse model.

Acute myeloid leukaemia results from the neoplastic transformation of haematopoietic stem cells. Although advances have been made in its treatment, the mortality rate remains high. As a result, therapeutic alternatives continue to be explored. In this study, we present evidence that suggests that casein, the principal protein in milk, possesses significant antileukaemic properties. We investigated whether casein inhibited the in vitro proliferation and induced the apoptosis of the mouse myelomonocytic leukaemia cell line WEHI-3. By contrast, under identical conditions, casein markedly promotes the proliferation of mouse normal mononuclear bone marrow cells. Since the selective elimination of leukaemia cells is an ideal therapeutic strategy, we also evaluated the antileukaemic potential of casein in vivo. The results showed that casein increases the survival of mice bearing WEHI-3-induced tumours, suggesting that this molecule is also capable of inhibiting the proliferation of these cells in vivo. The evidence that casein inhibited cell proliferation and induced apoptosis in leukaemia cells in vitro, but increased survival in vivo in a leukaemia mouse model, indicates that casein may be useful in leukaemia therapy.

Sodium caseinate induces mouse granulopoiesis.

OBJECTIVE AND DESIGN: Sodium caseinate (CasNa) induces differentiation and M-CSF production in mouse band granulocytes in vitro; however, it is not yet known if this molecule can also induce the proliferation and activation of the granulocyte lineage in vivo. In this work we evaluated the induction in vivo of granulopoiesis and the activation of granulocytes in mice treated with CasNa. MATERIAL OR SUBJECTS: BALB/c male mice 8-12 weeks old were used. TREATMENT: The animals were inoculated intraperitoneally with 1 ml of CasNa (10% in PBS p/v) four times (every 48 h). METHODS: Granulocyte proliferation was evaluated by flow cytometry; activation was evaluated by phagocytic indices. The cytokine was measured using an ELISA assay. RESULTS: We show that CasNa increased bone marrow granulopoiesis percentage (38.35 ± 10.88 vs. 64.94 ± 34.14 BrdU+/Gr-1+ cells) and the granulocytes generated presented increased phagocytic indices (0.3 ± 0.1 vs. 0.6 ± 0.11, p < 0.05). We also show that G-CSF (974 ± 411 vs. 3189 ± 350 pg/ml, p < 0.05) and GM-CSF increased in serum, but only G-CSF in bone marrow plasma. CONCLUSIONS: CasNa induces granulopoiesis with functional granulocytes, suggesting that this molecule could be an innate immune system activator.