Cellular mechanisms underlying the effects of sucralose on keratinocyte proliferation and its contributing roles in epidermal regeneration

Abstract

The main objectives of this study are to investigate the effects of sucralose on skin wound healing acceleration, UVB-induced epidermal epithelial damage, and to identify its underlying mechanisms of action. Sucralose significantly increased wound healing with an EC<inf>50</inf> of 30.47 μM, a maximal effect being observed at 100 μM. In addition, sucralose failed to induce wound healing in mitomycin C-primed HaCaT cell monolayers. Sucralose significantly increased keratinocyte proliferation and prevented UVB-induced cell death. These effects were suppressed by inhibitions of protein kinase A (PKA), AMP-activated protein kinase (AMPK), sirtuin-1 (SIRT-1), and extracellular signal-regulated kinase (ERK). Sucralose-induced AMPK phosphorylation was fully abolished by pretreatment with a PKA inhibitor. Sucralose-induced ERK phosphorylation was suppressed by inhibitors of AMPK and SIRT-1. Effect of sucralose-induced SIRT-1 activity was attenuated by PKA and AMPK inhibitor. Sucralose promotes wound healing and reduces keratinocyte death after UVB exposure by increasing cell proliferation via PKA/AMPK/SIRT-1/ERK-dependent mechanisms.