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Synthestic estrone derivatives as anticancer agents and as suppressors of hypoxia‐inducible factor‐1alpha in breast, prostate and glioma cancer cell lines
Author(s) -
Alokail Majed Saleh
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.678.1
Subject(s) - apoptosis , cell culture , cancer research , transfection , chemistry , transcription factor , u87 , hif1a , cancer cell , cell , cancer , biology , microbiology and biotechnology , glioma , medicine , angiogenesis , biochemistry , gene , genetics
Hypoxia‐inducible factor‐1 alpha (HIF‐1á) is the main transcriptional factor activated by hypoxia and it plays a key role in reprogramming tumor growth. HIF‐1á inhibition represent an important target for antitumor intervention with pharmacologic agents and a possible role for HIF‐1á in the modulation of apoptosis. In order to study how HIF‐1á can modulate apoptosis, we analyzed in this study 63 of synthestic estrone (Peptidylestrone, Alkylamino and Alkylthioacetylamino) derivatives in MDA231, MCF7 breast cancer cell lines and PC3 prostate cancer cell lines, in addition to HIF‐1á transfected U251 human glioblastoma cell line. All cell lines were incubated at 16 hours under normoxia with or without CoCl2 (a chemical inducer of HIF‐1á). Our data have shown many of these derivatives significantly decreased HIF‐1á expression in the presence of CoCl2. These derivatives have also shown significant increase in apoptosis in all cell lines. These derivatives also suppress HIF‐1á gene expression in the presence of CoCl2 in all cancer cells in addition to HIF‐1á transfected U251 human glioblastoma cell line. In conclusion, our preliminary data suggested more experiments are needed to define if thease derivatives modulate the HIF‐1á role in cell death pathway via different transcription factors depending on the cellular context and to determine the exact mechanism of these derivatives in cancer cell apoptosis effects.