Molecular and cellular effects of hydroxy-1,4 naphthoquinones used in dermatological and cosmetic applications on human protein tyrosine phosphatase PTP1B in human keratinocytes.

The hydroxy-1,4-naphthoquinones-lawsone, juglone, and plumbagin-widely used in dermatological and cosmetic applications, exhibit a broad spectrum of biological activities, including notable cytotoxic effects. Of the various cellular processes these quinones influence, signaling pathways hold utmost significance. This study elucidates the impact of lawsone, juglone, and plumbagin on a key tyrosine phosphatase, PTP1B, in vitro or within keratinocyte cell lines. Additionally, we assessed the phosphorylation status of EGFR and its subsequent consequences on cell migration. Our results reveal that juglone and plumbagin, but not lawsone, irreversibly inhibit PTP1B enzyme activity by up to 75% through modification of its catalytic cysteine 215 residue. These quinones also lead to an average of 3-fold increase in EGFR phosphorylation. These findings offer new insights into the molecular mechanisms through which hydroxy-1,4-naphthoquinones of dermatological or cosmetic interest modulate critical signaling pathways. SIGNIFICANCE STATEMENT: Hydroxy-1,4-naphthoquinones such as lawsone, juglone, and plumbagin are widely used in dermatological applications, yet their precise molecular and cellular effects remain underexplored. This study reveals that juglone and plumbagin irreversibly inhibit the phosphatase PTP1B by targeting its catalytic cysteine, leading to enhanced EGFR phosphorylation. These findings provide critical insights into how these compounds modulate key signaling pathways, advancing our understanding of their potential therapeutic applications in skin repair and diseases involving dysregulated cell signaling.