Document Detail


Delphinidin, a dietary antioxidant, induces human epidermal keratinocyte differentiation but not apoptosis: studies in submerged and three-dimensional epidermal equivalent models.
MedLine Citation:
PMID:  23614741     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Delphinidin (Del), [3,5,7,3'-,4'-,5'-hexahydroxyflavylium], an anthocyanidin and a potent antioxidant abundantly found in pigmented fruits and vegetables exhibits proapoptotic effects in many cancer cells. Here, we determined the effect of Del on growth, apoptosis and differentiation of normal human epidermal keratinocytes (NHEKs) in vitro in submerged cultures and examined its effects in a three-dimensional (3D) epidermal equivalent (EE) model that permits complete differentiation reminiscent of in vivo skin. Treatment of NHEKs with Del (10-40 μm; 24-48 h) significantly enhanced keratinocyte differentiation. In Del-treated cells, there was marked increase in human involucrin (hINV) promoter activity with simultaneous increase in the mRNA and protein expressions of involucrin and other epidermal differentiation markers including procaspase-14 and transglutaminase-1 (TGM1), but without any effect on TGM2. Del treatment of NHEKs was associated with minimal decrease in cell viability, which was not associated with apoptosis as evident by lack of modulation of caspases, apoptosis-related proteins including Bcl-2 family of proteins and poly(ADP-ribose) polymerase cleavage. To establish the in vivo relevance of our observations in submerged cultures, we then validated these effects in a 3D EE model, where Del was found to significantly enhance cornification and increase the protein expression of cornification markers including caspase-14 and keratin 1. For the first time, we show that Del induces epidermal differentiation using an experimental system that closely mimics in vivo human skin. These observations suggest that Del could be a useful agent for dermatoses associated with epidermal barrier defects including aberrant keratinization, hyperproliferation or inflammation observed in skin diseases like psoriasis and ichthyoses.
Authors:
Jean Christopher Chamcheu; Farrukh Afaq; Deeba N Syed; Imtiaz A Siddiqui; Vaqar M Adhami; Naghma Khan; Sohinderjit Singh; Brendan T Boylan; Gary S Wood; Hasan Mukhtar
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental dermatology     Volume:  22     ISSN:  1600-0625     ISO Abbreviation:  Exp. Dermatol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-25     Completed Date:  2013-11-07     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  9301549     Medline TA:  Exp Dermatol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  342-8     Citation Subset:  IM    
Copyright Information:
© 2013 John Wiley & Sons A/S.
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MeSH Terms
Descriptor/Qualifier:
Anthocyanins / pharmacology*
Antioxidants / pharmacology*
Apoptosis / drug effects
Caspases / metabolism
Cell Culture Techniques / methods
Cell Differentiation / drug effects
Cell Proliferation / drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Epidermis / cytology
Foreskin / cytology
Fruit / chemistry
Gene Expression / drug effects
Humans
Infant, Newborn
Keratinocytes / cytology*,  drug effects*
Male
Organ Culture Techniques / methods
Promoter Regions, Genetic / physiology
Protein Precursors / genetics
Vegetables / chemistry
Grant Support
ID/Acronym/Agency:
P30 CA013148/CA/NCI NIH HHS; P30 CA014520/CA/NCI NIH HHS; R01 AR059742/AR/NIAMS NIH HHS; R01 AR059742/AR/NIAMS NIH HHS; R21 AT004966/AT/NCCAM NIH HHS; R21 AT004966/AT/NCCAM NIH HHS; T32 AR055893/AR/NIAMS NIH HHS; T32AR055893/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Anthocyanins; 0/Antioxidants; 0/Protein Precursors; 13270-61-6/delphinidin; 60108-77-2/involucrin; EC 3.4.22.-/CASP14 protein, human; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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