title: Phytochemicals as Innovative Therapeutic Tools against Cancer Stem Cells.
abstract: The theory that several carcinogenetic processes are initiated and sustained by cancer stem cells (CSCs) has been validated, and specific methods to identify the CSCs in the entire population of cancer cells have also proven to be effective. This review aims to provide an overview of recently acquired scientific knowledge regarding phytochemicals and herbal extracts, which have been shown to be able to target and kill CSCs. Many genes and proteins that sustain the CSCs' self-renewal capacity and drug resistance have been described and applications of phytochemicals able to interfere with these signaling systems have been shown to be operatively efficient both in vitro and in vivo. Identification of specific surface antigens, mammosphere formation assays, serial colony-forming unit assays, xenograft transplantation and label-retention assays coupled with Aldehyde dehydrogenase 1 (ALDH1) activity evaluation are the most frequently used techniques for measuring phytochemical efficiency in killing CSCs. Moreover, it has been demonstrated that EGCG, curcumin, piperine, sulforaphane, β-carotene, genistein and the whole extract of some plants are able to kill CSCs. Most of these phytochemicals act by interfering with the canonical Wnt (β-catenin/T cell factor-lymphoid enhancer factor (TCF-LEF)) pathway implicated in the pathogenesis of several cancers. Therefore, the use of phytochemicals may be a true therapeutic strategy for eradicating cancer through the elimination of CSCs.
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino (PU) 61029, Italy. emanuele.scarpa@uniurb.it.
authors.forename: Emanuele-Salvatore
authors.initials: ES
authors.lastname: Scarpa
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino (PU) 61029, Italy. paolino.ninfali@uniurb.it.
authors.forename: Paolino
authors.initials: P
authors.lastname: Ninfali
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D064209:Phytochemicals / Q000633:toxicity*; D050697:Retinal Dehydrogenase / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D064209:Phytochemicals; D051153:Wnt Proteins; D051176:beta Catenin; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
keywords: cancer stem cells; chemoprevention; herbal extracts; metastases; molecular mechanisms; phytochemicals; self-renewal; therapeutic agents