Novel antitumor mechanisms of curcumin: implication of altered tumor metabolism, reconstituted tumor microenvironment and augmented myelopoiesis
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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.
KeywordsCurcumin Anti-tumor Tumor metabolism Myelopoiesis Macrophage differentiation Tumor microenvironment
The author is grateful to the Department of Botany and Microbiology, HNB Garhwal University, India for facilities required for preparing this manuscript.
- Baniyash M, Sade-Feldman M, Kanterman J (2013) Chronic inflammation and cancer: suppressing the suppressors. Cancer Immunol Immunother (Epub ahead of print)Google Scholar
- Catalano V, Turdo A, Di Franco S, Dieli F, Todaro M, Stassi G (2013) Tumor and its microenvironment: a synergistic interplay. Semin Cancer Biol 23:522-532Google Scholar
- Chen CC, Sureshbabul M, Chen HW, Lin YS, Lee JY, Hong QS, et al. (2013) Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin Upregulation in Colorectal Cancer. Evid Based Complement Alternat Med 2013:541695Google Scholar
- Draghiciu, O, Nijman, HW, Daemen, T (2011) From tumor immunosuppression to eradication: targeting homing and activity of immune effector cells to tumors. Clin Dev Immunol 2011:439053Google Scholar
- Gostner J, Ciardi C, Becker K, Fuchs D, Sucher R (2014) Immunoregulatory impact of food antioxidants. Curr Pharm Des 20:840–849Google Scholar
- Hasima N, Aggarwal BB (2014) Targeting proteasomal pathways by dietary curcumin for cancer prevention and treatment. Curr Med Chem 21(14):1583–94Google Scholar
- Kaefer CM, Milner JA (2011) Herbs and spices in cancer prevention and treatment. In: Benzie IFF, Wachtel-Galor S (eds) Herbal medicine: biomolecular and clinical aspects, 2nd edn. CRC Press, Boca Raton, FL (Chapter 17)Google Scholar
- Nagaraju GP, Zhu S, Wen J, Farris AB, Adsay VN, Diaz R, et al. (2013) Novel synthetic curcumin analogues EF31 and UBS109 are potent DNA hypomethylating agents in pancreatic cancer. Cancer Lett 341:195–203Google Scholar
- Ravindran J, Subbaraju GV, Ramani MV, Sung B, Aggarwal BB (2010) Bisdemethylcurcumin and structurally related hispolon analogues of curcumin exhibit enhanced prooxidant, anti-proliferative and anti-inflammatory activities in vitro. Biochem Pharmacol 79:1658–1666PubMedCentralPubMedCrossRefGoogle Scholar