Evaluation of the potential anti-carcinogenic effects of re- expressing and/or stimulating estrogen receptor-beta in the prostate cancer cell line PC3 / Mohamed Hemdan Nour Eldin ; Supervised Tarek Mohamed Kamal Motawi , Hebat Allah Abdelmoeti Mohamed Darwish , Iman Hassan Diab

Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Biochemistry

Background: It is now believed that estrogens act as key factors in prostate biology, influencing normal development, cellular proliferation and differentiation as well as cancer development and progression. Estrogens exert their actions through two distinct estrogen receptors, which are referred to as ER-Ü and ER-Ý. In the majority of estrogen-sensitive tissues including prostate, ER-Ý has exhibited tumor suppressive activities through diverse approaches. Whereas, other studies described ER-Ý to exert cancer-promoting actions. ER-Ý expression appears to be lost during prostate cancer progression through hypermethylation mechanism. Interestingly, epigenetic drugs such as 5-aza-2{u2032}-deoxycytidine (5-AZAC) and Trichostatin A (TSA) showed efficacy in restoring ER-Ý expression in prostate cancer cells. Aim: The current study was designed to explore the possible anti-carcinogenic actions resulting from co-treatment of PC-3 cell line with 5-AZAC and TSA, exploiting ER-Ý1 re-expression through targeting it with specific agonist, Diarylpropionitrile (DPN). Methods: To achieve this goal, PC-3 cells were treated with 5-AZAC, TSA, DPN and combinations thereof. Subsequently, cells were subjected to proliferation assays. ER-Ý1 expression was analyzed by qRT-PCR, while enzyme-linked immunosorbent assay (ELISA) was employed for evaluating protein levels of active caspase-3, cyclin D1, Ý-catenin in cell lysates and VEGF in culture medium

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