Destroying the Shield of Cancer Stem Cells: Natural Compounds as Promising Players in Cancer Therapy

Abstract

In a scenario where eco-sustainability and a reduction in chemotherapeutic drug waste are certainly a prerogative to safeguard the biosphere, the use of natural products (NPs) represents an alternative therapeutic approach to counteract cancer diseases. The presence of a heterogeneous cancer stem cell (CSC) population within a tumor bulk is related to disease recurrence and therapy resistance. For this reason, CSC targeting presents a promising strategy for hampering cancer recurrence. Increasing evidence shows that NPs can inhibit crucial signaling pathways involved in the maintenance of CSC stemness and sensitize CSCs to standard chemotherapeutic treatments. Moreover, their limited toxicity and low costs for large-scale production could accelerate the use of NPs in clinical settings. In this review, we will summarize the most relevant studies regarding the effects of NPs derived from major natural sources, e.g., food, botanical, and marine species, on CSCs, elucidating their use in pre-clinical and clinical studies.

Keywords: adjuvant treatments; alkaloids; cancer stem cells; drug resistance; flavonoids; natural products; polyphenols.

Figure 1

Natural products destroy the shield of CSCs. Radio- and chemotherapy target differentiated cancer cells, which represent most cells within the tumor mass, sparing the CSC subpopulation, characterized by the high expression of ABC transporters, anti-apoptotic molecules, and detoxification enzymes and the aberrant activation of stemness pathways and DNA repair machinery (left part). Natural products derived from different sources (marine, food, and botanical compounds) are able to reduce CSC features and increase their sensitivity to radio- and chemotherapy (right part). DCs, differentiated cells; CSC, cancer stem cell; ABC, ATP-binding cassette.