Background: Cancer Stem Cells (CSCs) are the subpopulation of cancer cells which are directly
involved in drug resistance, metastases to distant organ and cancer recurrence.
Methods: A systematic literature search was conducted through various electronic databases including, Pubmed,
Scopus, Google scholar using the keywords "cancer stem cells" and "natural compounds" in the present study.
Articles published between 1999 and 2019 were reviewed. All the expositions concerning CSCs associated
cancer pathogenesis and therapy resistance, as well as targeting these properties of CSCs by natural compounds
were selected for the current study.
Results: Natural compounds have always been thought as a rich source of biologically active principles, which
target aberrantly activated signaling pathways and other modalities of CSCs, while tethering painful side effects
commonly involved in the first-line and second-line chemo-radiotherapies. In this review, we have described the
key signaling pathways activated in CSCs to maintain their survival and highlighted how natural compounds
interrupt these signaling pathways to minimize therapy resistance, pathogenesis and cancer recurrence properties
of CSCs, thereby providing useful strategies to treat cancer or aid in cancer therapy improvement. Like normal
stem cells, CSCs rely on different signaling pathways and other properties for their maintenance. Therefore, the
success of cancer treatment depends on the development of proper anti-neoplastic drugs capable of intercepting
those signaling pathways as well as other properties of CSCs in order to eradicate this evasive subpopulation of
Conclusion: Compounds of natural origin might act as an outstanding source to design novel therapies against
cancer stem cells.