Abstract
Geoditin A, an isomalabaricane triterpene isolated from marine sponge Geodia japonica, has been demonstrated to induce apoptosis in leukemia HL60 cells and human colon HT29 cancer cells through an oxidative stress, a process also interfering with normal melanogenesis in pigment cells. Treatment of murine melanoma B16 cells with geoditin A decreased expression of melanogenic proteins and cell melanogenesis which was aggravated with adenylate cyclase inhibitor SQ22536, indicating melanogenic inhibition was mediated through a cAMP-dependent signaling pathway. Immunofluorescence microscopy and glycosylation studies revealed abnormal glycosylation patterns of melanogenic proteins (tyrosinase and tyrosinase-related protein 1), and a co-localization of tyrosinase with calnexin (CNX) and lysosome-associated membrane protein 1 (LAMP-1), implicating a post-translational modification in the ER and a degradation of tyrosinase in the lysosome. Taken together, potent anti-melanogenic property and the relatively low cytotoxicity of geoditin A have demonstrated its therapeutic potential as a skin lightening agent.
Highlights
Melanocytes are the major cell population in the skin epidermis which is responsible for melanin production and pigmentation of skin and hair
Geoditin A (Figure 1) is an isomalabaricane triterpene isolated from a South China Sea sponge, Geodia japonica [16]
Our previous study has demonstrated a potent cytotoxicity of geoditin A against human leukemia HL60 cells (IC50 = 3 μg/mL) [15], but mild to human colon carcinoma HT29 cells (IC50 = 20 μg/mL) [14]
Summary
Melanocytes are the major cell population in the skin epidermis which is responsible for melanin production and pigmentation of skin and hair. Reduction of MITF binding to the promoters of these melanogenic proteins results in a decrease of cell pigmentation. An excessive ROS production causes damage of DNA, proteins and lipids, resulting in apoptosis and cell death. Intracellular ROS at sublethal concentrations induce melanogenesis [8] through activation of apurinic/apyrimidinic endonuclease (APE) for oxidative DNA damage repair [9,10] and promotion of cell survival via MITF pathway [9]. Our previous studies have demonstrated geoditin A being a potent inducer of oxidative stress and apoptosis in HT29 cells [14] and HL60 cells [15] It is the objective in this study to investigate if this oxidative stress might interfere with tyrosinase activity and melanogenesis in murine B16 melanoma cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
