Invited ReviewThe use of plant-derived bioactive compounds to target cancer stem cells and modulate tumor microenvironment

- Cancer stem cells (CSCs) are chemo-radiotherapy resistant, causing tumor relapse.
- CSCs are known to reside within specific hypoxic and acidic tumor niches.
- Phytocompounds affect CSC self-renewal, metabolism and microenvironment.
- Phytocompounds might be exploited for cancer prevention and treatment.

In the last decades cancer has been considered as an epigenetic dysfunction, given the profound role of diet and lifestyle in cancer prevention and the determination of cancer risk. A plethora of recent publications have addressed the specific role of several environmental factors, such as nutritional habits, behavior, stress and toxins in the regulation of the physiological and cancer epigenome. In particular, plant-derived bioactive nutrients have been seen to positively affect normal cell growth, proliferation and differentiation and also to revert cancer related epigenetic dysfunctions, reducing tumorigenesis, preventing metastasis and/or increasing chemo and radiotherapy efficacy. Moreover, virtually all cancer types are characterized by the presence of cancer stem cell (CSC) subpopulations, residing in specific hypoxic and acidic microenvironments, or niches, and these cells are currently considered responsible for tumor resistance to therapy and tumor relapse. Modern anti-cancer strategies should be designed to selectively target CSCs and modulate the hypoxic and acidic tumor microenvironment, and, to this end, natural bioactive components seem to play a role. This review aims to discuss the effects elicited by plant-derived bioactive nutrients in the regulation of CSC self-renewal, cancer metabolism and tumor microenvironment.