Norah Mobarki,
College of Medicine University of Sharjah, UAE
Title: The role of oxysterols as selective estrogen receptor modulators (serms) at promoting tumor growth in adrenocortical carcinoma
Biography
Biography: Norah Mobarki,
Abstract
Adrenocortical carcinoma (ACC) is an aggressive and rare endocrine malignant with very limited treatment options at present. Besides, its recurrence rate is high and can occur in a short following period. ACC is a steroidogenesis cancer produces steroid hormones, that all share cholesterol as a key building unit. Thus, cholesterol active metabolites (oxysterols) could potentially interfere these steroids pathways and produce different cellular modifications through different receptors, included ERs. In ER+ breast cancer cells, oxysterols (i.e. 27Hydroxy Cholesterol) promote cell proliferation through estrogen receptor alpha ERα. Therefore oxysterols as selective estrogen receptor modulators (SERMs), we hypothesized that they could act similarly via ERs in ACC cells (H295R) and promote cell growth. In this study, H295R cells were treated for 24-h with (27HC) at various doses (0, 10, 20, 40, 80 uM) alone or combined with hydroxyl-tamoxifen (10uM OHT) or/ and 10nM 17-β estradiol (E2) to investigate the proliferative effect. The same treatment scheme was applied on MCF7 breast cancer cells. The principle experimental technique was crystal violet staining in which cells growth was measured via spectrophotometer at 550nm. The finding showed that 27HC plays a role at stimulating cell division on H295R cells, however, this effect is being further enhanced in the presence of other agents: E2 and OHT. For MCF7 control cells, the outcomes were correlated to a previous work that 27HC stimulates cell proliferation and OHT inhibits tumor formation. Overall, 27HC showed an expected effect, whereas, OHT unexpectedly induce cell density. Therefore, further work should consider the unexpected stimulatory effect of OHT and its mechanistic pathway, prior to suggesting it as an anti-estrogenic drug in ACC setting.