Depigmenting Effects of Calcium d‐Pantetheine‐S‐Sulfonate on Human Melanocytes

Abstract

The effects of calcium D-pantetheine-S-sulfonate (PaSSO3Ca) on human pigmentation were examined by in vitro assays using two types of human melanocytes: normal adult melanocytes (HNM) and M4Be melanoma cells. The compound, when added to a culture medium at doses indicating no cytotoxicity, causes a visually recognizable, reversible loss of pigment in both types of cells. Determination of melanin content, incorporation of 14C-DOPA into melanins and tyrosinase activities demonstrated that treatment of these cells with PaSSO3Ca resulted in a marked decrease in all three areas. When homogenates of these cells were assayed with lectins, the glycosylation pattern was modified, as tyrosinase activities were reduced in the cells treated with the compound. Immunoprecipitation of tyrosinase and tyrosinase-related protein 1 (Tyrp1 or TRP1) in cells incubated with radioactive glucosamine disclosed that glucosamine uptake by these enzymes was apparently increased, suggesting structural alterations in their sugar moieties. It is also noted that PaSSO3Ca is analogous in its chemical structure to Coenzyme A (CoA), which plays an important role in the intracellular transport of proteins. Based on these findings, it is likely that the compound exerts its depigmenting effects in human pigment cells through the modification of glycosylation of tyrosinase and TRP1, which are key enzymes for melanogenesis.

Inhibitory effect of piperlonguminine on melanin production in melanoma B16 cell line by downregulation of tyrosinase expression

“…This study demonstrated that piperlonguminine could downregulate α ‐MSH‐induced tyrosinase expression at the transcription level via a decrease of CREB phosphorylation, which is a rare mechanism for depigmenting efficacy. Several depigmenting agents have been also reported with diverse mechanisms of interference on melanin synthesis and deposition; arbutin and kojic acid targeting for tyrosinase activity (Kahn, 1995; Maeda and Fukuda, 1996), α ‐linolenic acid for tyrosinase degradation (Ando et al., 1998), RWJ‐50353 for protease‐activated receptor 2‐mediated melanosome transfer (Seiberg et al., 2000), and calcium D‐pantetheine‐S‐sulfonate for tyrosinase glycosylation (Franchi et al., 2000).…”

Chemical and Instrumental Approaches to Treat Hyperpigmentation

“…Glucosamine or tunicamycin, specific inhibitors of lipid carrier‐dependent glycosylation of protein, have been found to induce, in melanoma cells, a marked loss of pigmentation associated with ultrastructural alterations of melanogenic compartments (19). Calcium d ‐pantetheine‐ S‐sulphonate (PaSSO 3 Ca), probably through the alteration of tyrosinase and TRP‐1 glycosylation, causes an inhibition of melanogenic enzymes, without modifying their expression, and produces a reversible loss of pigmentation in normal human melanocytes and in melanoma cell lines (20).…”

Mechanisms Regulating Skin Pigmentation: The Rise and Fall of Complexion Coloration

“…In a distinct study by Choi et al , treatment of HM3KO melanoma cells with deoxynojirimycin, a α-glucosidase inhibitor that disrupts early ER N -glycan processing, and deoxymannojirimycin, an inhibitor of α-1,2-mannosidase which are thought to be responsible for late glycan processing, showed inhibition of glycosylation, transportation of tyrosinase to the melanosome and melanin synthesis [42]. Other factors explored for their ability to modulate tyrosinase glycosylation include calcium d -pantetheine- S -sulfonate [43], ferritin [44] and glutathione [45]. Glutathione induced inhibition of tyrosinase glycosylation, blocks the maturation and transfer of tyrosinase from GERL (Golgi-endoplasmic reticulum-lysosome)-coated vesicles to the pre-melanosome.…”