title: Glycyrrhizic acid attenuates stem cell-like phenotypes of human dermal papilla cells.
abstract: BACKGROUND
  Although the growth of unwanted hair or hirsutism is a harmless condition, many people find it bothersome and embarrassing. Maintaining stem cell features of dermal papilla cells is a critical biological process that keeps the high rate of hair growth. Glycyrrhizic acid has been reported to impair hair growth in some studies; however, its underlying mechanism has not yet been investigated.
  
  
  OBJECTIVE
  This study aimed to explore the effect and underlying mechanism of glycyrrhizic acid on stemness of human dermal papilla cells.
  
  
  METHODS
  The stem cell molecular markers, epithelial to mesenchymal markers and Wnt/β-catenin-associated proteins of human dermal papilla cell line and primary human dermal papilla cells were analysed by western blot analysis and immunocytochemistry.
  
  
  RESULTS
  The present study demonstrated that glycyrrhizic acid significantly depressed the stemness of dermal papilla cells in dose- and time-dependent manners. Clonogenicity and stem cell markers in the glycyrrhizic acid-treated cells were found to gradually decrease in the culture in a time-dependent manner. Our results demonstrated that glycyrrhizic acid exerted the stem cell suppressing effects through the interruption of ATP-dependent tyrosine kinase/glycogen synthase kinase3β-dependent mechanism which in turn down-regulated the β-catenin signalling pathway, coupled with decreased its down-stream epithelial-mesenchymal transition and self-renewal transcription factors, namely, Oct-4, Nanog, Sox2, ZEB1 and Snail. The effect of glycyrrhizic acid on the reduction of stem cell features was also observed in the primary dermal papilla cells directly obtained from human hair follicles.
  
  
  CONCLUSIONS
  These results revealed a novel molecular mechanism of glycyrrhizic acid in regulation of dermal papilla cells and provided the evidence supporting the use of this compound in suppressing the growth of unwanted hair.
authors.affiliation: Pharmaceutical Technology (International) Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Chayanin
authors.initials: C
authors.lastname: Kiratipaiboon
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Parkpoom
authors.initials: P
authors.lastname: Tengamnuay
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand ; Cell-Based Drug and Health Product Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address: pithi.c@chula.ac.th.
authors.forename: Pithi
authors.initials: P
authors.lastname: Chanvorachote
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D018859:Hair Follicle / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D014157:Transcription Factors / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D014157:Transcription Factors; D019695:Glycyrrhizic Acid; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: Dermal papilla cell; Epithelial-mesenchymal transition; Glycogen synthase kinase3β; Glycyrrhizic acid; Stem cell; β-catenin