Despite the numerous recent advances made in conventional anticancer therapies, metastasis
and recurrence still remain the major problems in cancer management. The current treatment modalities
kill the bulk of the tumor, leaving cancer stem cells behind and therefore, the agents specifically
targeting this cancer initiating cell population may have important clinical implications. In this
review article, the data about the inhibitory action of flavonoids, both natural as well as their synthetic
derivatives, on the self-renewal capacity and survival of cancer stem cells of different origins are compiled
and analyzed. These data indicate that several plant secondary metabolites, including soy isoflavone
genistein, green tea catechins and a widely distributed flavonol quercetin, have the potential to suppress the stemness
markers and properties, traits of the epithelial-to-mesenchymal transition and migratory characteristics, being also able to
sensitize these cells to the standard chemotherapeutic drugs. These polyphenolic compounds act through multiple signal
transduction pathways, providing thus the maximal therapeutic response and offering some promise to be included in the
future cancer treatment schemes in combination with the conventional therapies. Such approach may give an important
contribution to the shift of cancer management from palliative to curative mode, likely leading to the disease-free survival.
Thus, flavonoids can serve as attractive candidates for novel anticancer agents by eliminating the roots of cancer.
Keywords: Cancer stem cells, chemosensitization, epithelial-to-mesenchymal transition, flavonoids, polyphenols, signal transduction
mechanisms, stemness markers.
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