Cancer stem cells: potential target for bioactive food components.
Cancer stem cells often have phenotypic and functional characteristics similar to normal stem cells including the properties of self-renewal and differentiation. Recent findings suggest that uncontrolled self-renewal may explain cancer relapses and may represent a critical target for cancer prevention. It is conceivable that the loss of regulatory molecules resulting from inappropriate consumption of specific foods and their constituents may foster the aberrant self-renewal of cancer stem cells. In fact, increasing evidence points to the network delivering signals for self-renewal from extracellular compartments to the nucleus including changes in stem cell environments, inducible expression of microRNAs, hyperplastic nuclear chromatin structures, and the on/off of differentiation process as possible sites of action for bioactive food components. Diverse dietary constituents such as vitamins A and D, genistein, (-)-epigallocatechin-3-gallate (EGCG), sulforaphane, curcumin, piperine, theanine and choline have been shown to modify self-renewal properties of cancer stem cells. The ability of these bioactive food components to influence the balance between proliferative and quiescent cells by regulating critical feedback molecules in the network including dickkopf 1 (DKK-1), secreted frizzled-related protein 2 (sFRP2), B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and cyclin-dependent kinase 6 (CDK6) may account for their biological response. Overall, the response to food components does not appear to be tissue or organ specific, suggesting there may be common cellular mechanisms. Unquestionably, additional studies are needed to clarify the physiological role of these dietary components in preventing the resistance of tumor cells to traditional drugs and cancer recurrence.
Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA. yk47s@nih.gov
Young S
YS
Kim
William
W
Farrar
Nancy H
NH
Colburn
John A
JA
Milner
D000470:Alkaloids / Q000494:pharmacology; D052117:Benzodioxoles / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002794:Choline / Q000494:pharmacology; D003474:Curcumin / Q000737:chemistry; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000378:metabolism; D004032:Diet; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D019833:Genistein / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D017879:Isothiocyanates; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D063150:Polycomb Repressive Complex 1; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology; D014801:Vitamin A / Q000494:pharmacology; D014807:Vitamin D / Q000494:pharmacology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
D000470:Alkaloids; D052117:Benzodioxoles; D002392:Catechin; D002794:Choline; D003474:Curcumin; D051361:Cyclin-Dependent Kinase 6; D019833:Genistein; D005971:Glutamates; D036341:Intercellular Signaling Peptides and Proteins; D017879:Isothiocyanates; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010880:Piperidines; D010936:Plant Extracts; D063150:Polycomb Repressive Complex 1; D053284:Polyunsaturated Alkamides; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D013454:Sulfoxides; D013861:Thiocyanates; D014801:Vitamin A; D014807:Vitamin D; D051153:Wnt Proteins; C069077:BMI1 protein, human; C501126:DKK1 protein, human; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C026166:theanine; C045651:epigallocatechin gallate; C016766:sulforaphane; C008922:piperine