Complexity of Tumor Microenvironment: Therapeutic Role of Curcumin and Its Metabolites

Abstract

The tumor microenvironment (TME) is a complex network of cellular and non-cellular components surrounding the tumor. The cellular component includes fibroblasts, adipocytes, endothelial cells, and immune cells, while non-cellular components are tumor vasculature, extracellular matrix and signaling molecules. The tumor cells have constant close interaction with their surrounding TME components that facilitate their growth, survival, and metastasis. Targeting a complex TME network and its interaction with the tumor can offer a novel strategy to disrupt cancer cell progression. Curcumin, from turmeric rhizome, is recognized as a safe and effective natural therapeutic agent against multiple diseases including cancer. Here the effects of curcumin and its metabolites on tumor-TME interaction modulating ability have been described. Curcumin and its metabolites regulate TME by inhibiting the growth of its cellular components such as cancer-associated adipocytes, cancer-associated fibroblast, tumor endothelial cells, tumor-stimulating immune cells, and inducing anticancer immune cells. They also inhibit the interplay of tumor cells to TME by suppressing non-cellular components such as extracellular matrix, and associated tumor promoting signaling-pathways. In addition, curcumin inhibits the inflammatory environment, suppresses angiogenic factors, and increases antioxidant status in TME. Overall, curcumin has the capability to regulate TME components and their interaction with tumor cells.

Acknowledgments

P.S greatly acknowledges the financial support from the DBT-Research Associateship Program in Life science and Biotechnology. B.C is supported by UGC-Junior Research Fellowship. We thank Shyanne Page-Hefley from the Department of Pediatrics for carefully proofreading the manuscript.

Author Contributions

S.P. contributed to the concept, design and to the writing of the manuscript. P.S. contributed to preparation of figure. B.C. contributed to literature search, and preparation of tables. A.K.S., A.A.C., R.L. reviewed and provided feedback in the manuscript designing and writing.

Conflicts of Interest

The authors declare no conflict of interests.

Funding

The author(s) reported there is no funding associated with the work featured in this article.