Moontlike induksie van outophagie en apoptose deur ‘n nuwe 17-Beta-Estradiol Analoog in slukdermkarsinoomselle

<div style="font-size: 12px; font-family: serif; left: 227.349px; top: 312.642px; transform: scale(1.08771, 1); transform-origin: 0% 0% 0px;" dir="ltr">Esofaguskanker (EK) is een van die 8 mees algemene kankers en weens die hoë sterftesyfer word</div><div style="font-size: 12px; font-family: serif; left: 227.349px; top: 328.642px; transform: scale(1.05659, 1); transform-origin: 0% 0% 0px;" dir="ltr">dit ook as die 6de hoogste mortaliteitskanker geklassifiseer. In huidige studies, is die</div><div style="font-size: 12px; font-family: serif; left: 530.488px; top: 344.642px; transform: scale(1.03558, 1); transform-origin: 0% 0% 0px;" dir="ltr">in vitro effek van C19, ‘n unieke 17-beta-estradiol analoog (0.2μM en blootstellingstyd van 24 uur) op die esofaguskarsinoom SNO sellyn getoets.</div

<i>In vitro</i> veranderinge in mitochondriale membraan potensiaal, aggresoom formasie en kaspase aktiwiteit deur `n nuwe 17-β-estradiol analoog in bors adenokarsinoomselle

<div style="font-size: 12px; font-family: serif; left: 543.465px; top: 340.284px; transform: scale(1.04355, 1); transform-origin: 0% 0% 0px;" dir="ltr">Die natuurlike metaboliet van estradiol, naamlik 2-metoksieëstradiol (2ME2) oefen antiproliferatiewe en anti-tumor effekte in vitro en <em>in vivo</em> uit met minimale of geen toksisiteit nie.</div

Sulphamoylated 2-Methoxyestradiol Analogues Induce Apoptosis in Adenocarcinoma Cell Lines

2-Methoxyestradiol (2ME2) is a naturally occurring estradiol metabolite which possesses antiproliferative, antiangiogenic and antitumor properties. However, due to its limited biological accessibility, synthetic analogues have been synthesized and tested in attempt to develop drugs with improved oral bioavailability and efficacy. The aim of this study was to evaluate the antiproliferative effects of three novel in silico-designed sulphamoylated 2ME2 analogues on the HeLa cervical adenocarcinoma cell line and estrogen receptor-negative breast adenocarcinoma MDA-MB-231 cells. A dose-dependent study (0.1–25 μM) was conducted with an exposure time of 24 hours. Results obtained from crystal violet staining indicated that 0.5 μM of all 3 compounds reduced the number of cells to 50%. Lactate dehydrogenase assay was used to assess cytotoxicity, while the mitotracker mitochondrial assay and caspase-6 and -8 activity assays were used to investigate the possible occurrence of apoptosis. Tubulin polymerization assays were conducted to evaluate the influence of these sulphamoylated 2ME2 analogues on tubulin dynamics. Double immunofluorescence microscopy using labeled antibodies specific to tyrosinate and detyrosinated tubulin was conducted to assess the effect of the 2ME2 analogues on tubulin dynamics. An insignificant increase in the level of lactate dehydrogenase release was observed in the compounds-treated cells. These sulphamoylated compounds caused a reduction in mitochondrial membrane potential, cytochrome c release and caspase 3 activation indicating apoptosis induction by means of the intrinsic pathway in HeLa and MDA-MB-231 cells. Microtubule depolymerization was observed after exposure to these three sulphamoylated analogues