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Analysis of DNA in endometrial cancer cells treated with phyto-estrogenic compounds using comparative genomic
Sharon A O'Toole1, Brian L Sheppard, Orla Sheils
1Trinity Centre for Health Sciences, St. James's Hospital, Department of Obstetrics and Gynaecology, University of Dublin, Dublin, Ireland. shotoole@tcd.ie
Abstract:
The aim of this study was to identify genomic aberrations in endometrial cancer cells treated with the phyto-estrogenic compounds tectorigenin, irigenin and apigenin and to compare with those treated with beta-estradiol using array-based comparative genomic hybridisation (array CGH). The microarray contains 287 targets and includes telomeres, microdeletions, oncogenes and tumour suppressor genes and has increased mapping resolution compared to conventional CGH. An endometrial cancer cell line (Ishikawa) was cultured and treated with the phyto-estrogens. Treated cells were examined using the CGH microarray. Over 20 % of the array genes were aberrated in the cells treated with beta-estradiol, tectorigenin and irigenin compared to 3 % in those treated with the same concentration of apigenin. Protein kinase c zeta form, insulin, insulin receptor and protein-tyrosine phosphatase non-receptor-type 1 which are involved in insulin metabolism were aberrated by tectorigenin and irigenin. Apigenin may play a role in the treatment of endometrial cancer and in the treatment of postmenopausal women. Further studies in normal endometrium and primary endometrial cancer cells are needed to elucidate the role of the phyto-estrogens.
Insights
Phyto-estrogens like tectorigenin and irigenin caused genomic aberrations in endometrial cancer cells. Apigenin showed fewer aberrations, suggesting potential in endometrial cancer treatment.
Area of Science:
- Genomics
- Molecular Biology
- Endocrinology
Background:
- Endometrial cancer is a significant health concern.
- Phyto-estrogenic compounds are plant-derived molecules with estrogen-like activity.
- Understanding their impact on cancer cell genomics is crucial for therapeutic development.
Purpose of the Study:
- To identify genomic aberrations in endometrial cancer cells treated with phyto-estrogens (tectorigenin, irigenin, apigenin).
- To compare these aberrations with those induced by beta-estradiol.
- To investigate the potential role of apigenin in endometrial cancer treatment.
Main Methods:
- Utilized an endometrial cancer cell line (Ishikawa).
- Treated cells with tectorigenin, irigenin, apigenin, and beta-estradiol.
- Employed array-based comparative genomic hybridization (array CGH) with a 287-target microarray.
Main Results:
- Beta-estradiol, tectorigenin, and irigenin induced genomic aberrations in over 20% of array genes.
- Apigenin treatment resulted in aberrations in only 3% of array genes.
- Tectorigenin and irigenin aberrated genes involved in insulin metabolism, including insulin receptor.
Conclusions:
- Apigenin exhibits a distinct genomic aberration profile compared to other tested phyto-estrogens and beta-estradiol.
- Apigenin shows promise for potential therapeutic applications in endometrial cancer, particularly for postmenopausal women.
- Further research involving normal endometrium and primary cancer cells is necessary to fully elucidate phyto-estrogen roles.
