Alpha-, beta- and kappa-caseins inhibit the proliferation of the myeloid cell lines 32D cl3 and WEHI-3 and exhibit different differentiation properties

We have recently shown that sodium caseinate (CasNa) was able to inhibit the proliferation of the myeloid cell line 32D cl3 in a non-toxic way, and that it also induced the expression of macrophage colony-stimulating factor (M-CSF). Casein is the main protein present in milk and is composed of alpha (α), beta (β) and kappa (κ) subunits. This work was undertaken to evaluate if any one casein is responsible for the proliferation and differentiation properties found for CasNa on myeloid cells. Taking into consideration that 32D cl3 cells are considered to be non-malignant and dependent on IL-3 for proliferation, we also included for this study a leukemic cell line, WEHI-3, that does not depend on any external growth factor for its proliferation in order to evaluate if the growth inhibitory effect of caseins is also present for malignant cells. Our results showed that all caseins were inhibitory for the proliferation of either 32D cl3 and WEHI-3 and that only the 32D cl3 cells were induced to differentiate into the monocyte-macrophage lineage. In order to evaluate if CasNa was able to inhibit the proliferation of other myeloid cells we used J774 and P388 and found that they were also inhibited. We also determined that the different caseins exhibit different differentiation properties, with α-casein being the only one able to induce the secretion of M-CSF. We consider this work to open a new field of research, where casein, or its components, can be studied for their possible role in hematopoiesis and on the inhibition of malignant cell proliferation for therapeutic use.