Elżbieta Fiedor1, Karolina Zajda1, Ewa L Gregoraszczuk2. 1. Department of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Kraków, Krakow, Poland. 2. Department of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Kraków, Krakow, Poland ewa.gregoraszczuk@uj.edu.pl.
Abstract
BACKGROUND/AIM: A common finding in cancer cells is the overexpression of histone deacetylases (HDACs), leading to altered expression and activity of numerous proteins involved in carcinogenesis. Considering that leptin can modulate the levels of HDACs, we hypothesised that leptin receptor antagonists can alter HDAC expression. MATERIALS AND METHODS: HDAC expression in cells exposed to leptin and leptin receptor antagonists (SHLA and Lan2) were evaluated in ovarian epithelial (OVCAR-3, CaOV3) and folliculoma (COV434, KGN) cells. RESULTS: Higher HDAC expression was found in epithelial compared to folliculoma cells. Leptin increased class I and II HDACs only in OVCAR-3 cells, and SHLA was more potent then Lan-2. In folliculoma cells, leptin only increased class II HDAC expression, Lan-2 was more potent than SHLA in the COV434 and neither antagonist affected the KGN cells. CONCLUSION: SHLA and Lan2 eliminate the negative effects of leptin on HDAC expression in a cell-type-dependent manner. This is the first report testing leptin receptor blockers as HDAC inhibitors in ovarian cancer cells. Copyright
BACKGROUND/AIM: A common finding in cancer cells is the overexpression of histone deacetylases (HDACs), leading to altered expression and activity of numerous proteins involved in carcinogenesis. Considering that leptin can modulate the levels of HDACs, we hypothesised that leptin receptor antagonists can alter HDAC expression. MATERIALS AND METHODS: HDAC expression in cells exposed to leptin and leptin receptor antagonists (SHLA and Lan2) were evaluated in ovarian epithelial (OVCAR-3, CaOV3) and folliculoma (COV434, KGN) cells. RESULTS: Higher HDAC expression was found in epithelial compared to folliculoma cells. Leptin increased class I and II HDACs only in OVCAR-3 cells, and SHLA was more potent then Lan-2. In folliculoma cells, leptin only increased class II HDAC expression, Lan-2 was more potent than SHLA in the COV434 and neither antagonist affected the KGN cells. CONCLUSION: SHLA and Lan2 eliminate the negative effects of leptin on HDAC expression in a cell-type-dependent manner. This is the first report testing leptin receptor blockers as HDAC inhibitors in ovarian cancer cells. Copyright
Authors: Euan A Stronach; Albandri Alfraidi; Nona Rama; Christoph Datler; James B Studd; Roshan Agarwal; Tankut G Guney; Charlie Gourley; Bryan T Hennessy; Gordon B Mills; Antonello Mai; Robert Brown; Roberto Dina; Hani Gabra Journal: Cancer Res Date: 2011-05-13 Impact factor: 12.701