Delphinidin, a dietary antioxidant, induces human epidermal keratinocyte differentiation but not apoptosis: Studies in submerged and three-dimensional epidermal equivalent models.
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 and Hasan Mukhtar
Institution
Uni Wisconsin
Country
United States
Year
2013
Journal
Experimental Dermatology
Abstract
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 (NHEK) in vitro
in submerged cultures and examined its effects in a three-dimensional (3D) epidermal
equivalent 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
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 epidermal equivalent 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.