Ceramide Inhibits Cell Proliferation through Akt/PKB Inactivation and Decreases Melanin Synthesis in Mel-Ab Cells

• Published in: Pigment cell research Vol. 14; no. 2; pp. 110 - 115
• Main Authors: KIM, DONG-SEOK, KIM, SOOK-YOUNG, MOON, SEONG-JOON, CHUNG, JIN-HO, KIM, KYU-HAN, CHO, KWANG-HYUN, PARK, KYOUNG-CHAN
• Format: Journal Article
• Language: English
• Published: Copenhagen Munksgaard 01.04.2001
• Subjects: Animals; Cell Division - drug effects; Cell Line; Cell Survival - drug effects; Enzyme Activation - drug effects; Enzyme Inhibitors - pharmacology; Humans; Melanins - biosynthesis; Melanocytes - drug effects; Melanocytes - metabolism; Melanoma - drug therapy; Melanoma - metabolism; Melanoma - pathology; Mice; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Monophenol Monooxygenase - drug effects; Monophenol Monooxygenase - metabolism; Phosphorylation; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - drug effects; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Sphingosine - analogs & derivatives; Sphingosine - pharmacology
• ISSN: 0893-5785; 1600-0749
• DOI: 10.1034/j.1600-0749.2001.140206.x

Ceramide is a bioactive sphingolipid that mediates a variety of cell functions. However, the effects of ceramide on cell growth and the melanogenesis of melanocytes are not known. In the present study, we investigated the actions of cell‐permeable ceramide and its possible role in the signaling pathway of a spontaneously immortalized mouse melanocyte cell line, Mel‐Ab. Our results show that C2‐ceramide inhibits DNA synthesis in Mel‐Ab cells and G361 human melanoma cells in a dose‐dependent manner. Cell cycle analysis confirmed the inhibition of DNA synthesis by a reduction in the S phase. To investigate the ceramide signaling pathway, we studied whether C2‐ceramide is able to influence extracellular signal‐regulated kinase (ERK) and/or Akt/protein kinase B (PKB) activation. We demonstrated that phosphorylated Akt/PKB is decreased by C2‐ceramide, whereas phosphorylated ERK was only slightly affected. Therefore, the C2‐ceramide‐induced inactivation of Akt/PKB may be closely related to the reduced cell proliferation of Mel‐Ab cells. Furthermore, we assessed the effects of C2‐ceramide on the pigmentation of Mel‐Ab cells. The results obtained showed that the melanin content of cells was significantly reduced by C2‐ceramide at concentrations in the range of 1–10 μM, and that the pigmentation‐inhibiting effect of C2‐ceramide is much greater than that of kojic acid at 1–100 μM. In addition, we found that the activity of tyrosinase is reduced by C2‐ceramide treatment. Our results demonstrate that C2‐ceramide reduces the pigmentation of Mel‐Ab cells by inhibiting tyrosinase activity.