title: Influence of betulin and 28-O-propynoylbetulin on proliferation and apoptosis of human melanoma cells (G-361).
abstract: BACKGROUND
  Pentacyclic triterpenes are a group of compounds known to have anticancer activity. One of the best characterized triterpenes is betulin, which can be isolated from bark of birch trees and modified into new compounds with various interesting medical properties. Betulin is involved in activation of the caspase cascade and promotes cell death. The aim of the study was to investigate the effect of betulin and its acetylenic derivative, 28-O-propynoylbetulin, on proliferation and apoptosis in a human melanoma cell line.
  
  
  METHODS
  The G-361 melanoma cell line was used. To evaluate growth arrest and caspase-3 activity, cells were treated with betulin and its derivative at a wide range of concentrations from 0.1 to 10 μg/mL.
  
  
  RESULTS
  Betulin and 28-O-propynoylbetulin inhibited cell proliferation in a concentration-dependent manner. The cell cycle analysis revealed an increase of the sub-G1 cell fraction (representing dead cells) after incubation of cells with betulin and 28-O-propynoylbetulin. The observed cytotoxic effects were more pronounced for 28-O-propynoylbetulin. Activity of caspase-3 in 28-O-propynoylbetulin treated cells was nearly 2-fold greater compared to cells incubated with betulin.
  
  
  CONCLUSIONS
  Our results show that betulin and 28-O-propynoylbetulin were effective in inhibition of cell growth and induction of apoptosis in a human melanoma cell line. The addition of the propynoyl group at the C-28 hydroxyl group of betulin led to a greater proapoptotic and antiproliferative effect in comparison to unmodified betulin. These observations suggest that the obtained derivative is a potent anti-melanoma agent.
authors.affiliation: Department of Biopharmacy, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Orchel
authors.affiliation: Department of Biopharmacy, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kulczycka
authors.affiliation: Department of Biopharmacy, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Chodurek
authors.affiliation: Department of Organic Chemistry, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Bębenek
authors.affiliation: Department of Medical Genetics, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Borkowska
authors.affiliation: Department of Organic Chemistry, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Stanisław
authors.initials: S
authors.lastname: Boryczka
authors.affiliation: Department of Medical Genetics, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Kowalski
authors.affiliation: Department of Biopharmacy, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Dzierżewicz
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D014315:Triterpenes / Q000494:pharmacology*; D000094042:Lupanes; D000094062:Betulinic Acid
chemical_list: D000970:Antineoplastic Agents; D053148:Caspase 3; D014315:Triterpenes; C000589676:28-O-propynoylbetulin; D000094042:Lupanes; C002503:betulin; D000094062:Betulinic Acid