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In Association with
Effect of newly synthesized progesterone derivatives on apoptotic and metastatic pathway in MCF-7 breast cancer cells
2nd World Congress on Bio Summit & Molecular Biology Expo
Shaymaa M M Yahya, Mervat M Abd-Elhalim, Ghada H Elsayed and Abdo A Othman
National Research Centre, Egypt
Posters & Accepted Abstracts: J Biotechnol Biomater
Abstract
Background: Breast cancer is the second leading cause of mortality among women worldwide. Anticancer agents consisting of hybrid molecules are used to improve efficacy and reduce drug resistance. Alteration of different genes is involved in the development of cancer. Consequently, novel anticancer drugs with increased selectivity and specificity are required to overcome limitation of current drugs. A variety of synthetic steroid derivatives have been contrived, most these derivatives can interact with the steroid receptors because of a similarity of shape. Also, the investigation of modified steroid derivatives condensed with various heterocyclic rings has a great attention. Impaired apoptosis and metastasis are critical in cancer development and is a major barrier to effective treatment. Methods: Several progesterone derivatives were synthesized. The structure of the newly derivatives was elucidated and confirmed using the analytical and spectral data. The newly synthesized progesterone derivatives, compounds 1, 2, 3, 4, 5, 6 and 7 were tested for their cytotoxic effects against human breast cancer cells (MCF-7) using neutral red uptake assay. Using QRTPCR (Quantitative Real Time-Polymerase Chain Reaction), the expression levels of P53, P21, Cdc2, Bcl-2, Survivin, CCND1, VEGF, HIF-1�±, FGF-1, MMP-2, MMP-9, Ang-1 and Ang-2 genes were investigated. Results: All tested compounds showed low IC50 values that were comparable to that of tamoxifen. The most active compounds against MCF-7 cancer cell line was in the descending order of 5>1>2>6>4>7>3. The study revealed that all newly synthesized compounds down-regulated the expression levels of BCL-2, surviving, VEGF, Ang-2 and MMp-9. Compound 2-7 downregulated CCND1 gene expression, nevertheless, this was only significant in case of compounds 2, 3 and 6. However, P53 were up-regulated by compounds 3. Moreover, compound 1 significantly down-regulated MMP-2 and compound 3 and 7 significantly down-regulated FGF-1. Conclusion: This study introduced promising pro-apoptotic and anti-metastatic anticancer agents acting through the regulation of key regulators of apoptosis, cell cycle and metastasis related genes.Biography
Email: yahshay10@yahoo.com
