Novel antitumor mechanisms of curcumin: implication of altered tumor metabolism, reconstituted tumor microenvironment and augmented myelopoiesis

Curcumin, a product of turmeric plant (Curcuma longa), is widely recognized for its antitumor and anti-inflammatory actions. Multiple mechanisms mediate the antitumor actions of curcumin, involving modulation of cell signaling events, manifesting tumor cytostasis and cytotoxicity. However, until recent it was unclear if the antitumor actions of curcumin also implicate modulation of some crucial checkpoints of unique tumor-specific metabolic events and tumor growth regulatory components of tumor microenvironment (TME), which are the focus of emerging antitumor therapeutic strategies. Considering the indispensible role of these hallmarks of cancer in tumor progression, recent studies investigated if curcumin could also therapeutically target one or more of these driving forces of oncogenesis. Investigations strongly indicate that curcumin can alter glucose uptake and its metabolism in tumor cells, leading to an altered pH homeostasis and reversal of lactic acidosis, culminating in induction of apoptosis. Curcumin can also inhibit tumor progression by antagonizing pro-inflammatory cellular and biophysical parameters of TME. Further, curcumin exerts myelopoietic action, owing to the withdrawal of tumor-dependent toxicity and myelosuppression, improved expression of heme-oxygenase and alleviation of the inhibitory actions of anticancer drugs on bone marrow cells. This review compiles the present state of knowledge, with respect to the effect of this wonder drug on tumor metabolism, components of TME and myelopoiesis. The review also predicts the possible impact of these newly understood roles of curcumin in designing of novel therapeutic protocols against cancer.