Myelopotentiating effect of curcumin in tumor-bearing host: role of bone marrow resident macrophages

The present investigation was undertaken to study if curcumin, which is recognized for its potential as an antineoplastic and immunopotentiating agent, can also influence the process of myelopoiesis in a tumor-bearing host. Administration of curcumin to tumor-bearing host augmented count of bone marrow cell (BMC) accompanied by an up-regulated BMC survival and a declined induction of apoptosis. Curcumin administration modulated expression of cell survival regulatory molecules: Bcl2, p53, caspase-activated DNase (CAD) and p53-upregulated modulator of apoptosis (PUMA) along with enhanced expression of genes of receptors for M-CSF and GM-CSF in BMC. The BMC harvested from curcumin-administered hosts showed an up-regulated colony forming ability with predominant differentiation into bone marrow-derived macrophages (BMDM), responsive for activation to tumoricidal state. The number of F4/80 positive bone marrow resident macrophages (BMM), showing an augmented expression of M-CSF, was also augmented in the bone marrow of curcumin-administered host. In vitro reconstitution experiments indicated that only BMM of curcumin-administered hosts, but not in vitro curcumin-exposed BMM, augmented BMC survival. It suggests that curcumin-dependent modulation of BMM is of indirect nature. Such prosurvival action of curcumin is associated with altered T_H1/T_H2 cytokine balance in serum. Augmented level of serum-borne IFN-γ was found to mediate modulation of BMM to produce enhanced amount of monokines (IL-1, IL-6, TNF-α), which are suggested to augment the BMC survival. Taken together the present investigation indicates that curcumin can potentiate myelopoiesis in a tumor-bearing host, which may have implications in its therapeutic utility.