2-Methoxyestradiol-3,17,0,0-bis-sulfamate (2MEBM) induces two types of cell death in a cervical adenocarcinoma cell line

2-MEBM induced apoptosis and autophagy in HeLa cells and also disrupted the cellular microtubule network. This contributes to the understanding of the in vitro mechanism of action of 2MEBM as a potential anticancer drug.This paper was initially delivered at the Annual Congress of the Biological Sciences Division of the South African Academy for Science and Art, ARC-Plant Protection Research Institute, Roodeplaat, Pretoria, South Africa on 01 October 2010.http://www.satnt.ac.zaam2014ay201

Influence of estradiol analogue on cell growth, morphology and death in esophageal carcinoma cells

2-Methoxyestradiol-bis-sulphamate is a bis-sulphamoylated derivative of the naturally occurring 17-beta-estradiol metabolite namely 2-methoxyestradiol. 2-Methoxyestradiol-bis-sulphamate is regarded as a potential anticancer drug with increased antiproliferative activity when compared to 2-methoxyestradiol. The aim of this pilot in vitro study was to determine the influence of 2-methoxyestradiol-bis-sulphamate on cell growth, morphology and possible induction of certain types of cell death in the SNO esophageal carcinoma cell line. A dose-dependent study (0.2-1.0μM) was conducted with an exposure time of 24 hours. Data revealed that 2-methoxyestradiol-bis-sulphamate reduced cell numbers statistically significantly to 74% after exposure to 0.4μM of the drug. Morphological studies including light microscopy demonstrated hallmarks of apoptosis, while fluorescent microscopy revealed both the presence of apoptosis and autophagy as types of cell death being induced in SNO cells after 24 hours of exposure to 0.4μM 2-methoxyestradiol-bis-sulphamate.http://www.scielo.org.ar/scielo.php/script_sci_serial/lng_en/pid_0327-9545/nrm_is

In vitro evaluation of 2-methoxyestradiol-bis-sulphamate on cell growth, morphology, cell cycle progression and possible induction of types of cell death in an oesophageal carcinoma (sno) cell line

Autophagy and apoptosis were induced and therefore suggests a link between two types of cell deaths induced by this compound.This paper was initially delivered at the Annual Congress of the Biological Sciences Division of the South African Academy for Science and Art, ARC-Plant Protection Research Institute, Roodeplaat, Pretoria, South Africa on 01 October 2010.http://www.satnt.ac.zaam201

2-Methoxyestradiol-bis-sulphamate : a promising anticancer agent in an esophageal carcinoma (SNO) cell line

2-Methoxyestradiol-bis-sulphamate (2-MeOE2bisMATE) is a bis-sulphamoylated analogue of a biological estradiol metabolite, 2-methoxyestradiol (2ME2) with potential as an anticancer drug. The aim of this in vitro study was to evaluate the effects of 2-MeOE2bisMATE on alpha-tubulin structure, as well as its potential to induce apoptosis in an esophageal carcinoma (SNO) cell line using confocal microscopy, flow cytometry and spectrophotometry. 2-MeOE2bisMATE disrupted the microtubule network of SNO cells, arrested cells in metaphase and induced apoptosis. An increase in the number of cells present in sub-G1, mitochondrial membrane potential reduction and increased caspase 6 activity were observed. This in vitro study demonstrated new insights on the action mechanism of 2 MeOE2bisMATE in esophageal carcinoma (SNO) cells, since these activities have not been studied in esophageal carcinoma cells up to date. Future studies are warranted to further determine which gene and protein expression changes are induced by 2-MeOE2bisMATE in SNO cells.This research was supported by grants awarded to Professor AM Joubert (University of Pretoria) from the National Research Foundation (NRF), Cancer Association of South Africa (AK246), the Medical Research Council (AG374, AK076) and Research Committee of the University of Pretoria (Pretoria, South Africa).http://www.biomedres.infohb2016Physiolog

2-Methoxyestradiol-bis-sulphamate disrupts microtubule network, arrests cell cycle and induces apoptosis in an esophageal carcinoma cell line

Future in vitro studies into the mechanism of this potentially anticancer drug are warranted.This abstract was initially presented at the annual Biological Sciences Symposium, presented under the protection of the Suid-Afrikaanse Akademie vir Wetenskap en Kuns. The symposium was held at the University of Johannesburg on 01 October 2011.http://www.satnt.ac.z

The in vitro effects of compound-X on growth, morphology, the induction of autophagy and apoptosis, as well as cell cycle progression in a cervical adenocarcinoma cell line

It can be concluded that compound-X induced both autophagy and apoptosis as a means of cell death in HeLa cells.This abstract was initially presented at the annual Biological Sciences Symposium, presented under the protection of the Suid-Afrikaanse Akademie vir Wetenskap en Kuns. The symposium was held at the University of Johannesburg on 01 October 2011.http://www.satnt.ac.z

The in vitro effects of a sulphamoylated derivative of 2-methoxyestradiol on cell number, morphology and alpha-tubulin disruption in cervical adenocarcinoma (HeLa) cells

2-Methoxyestradiol (2ME2) is an endogenous metabolite of estrogen that has both antiangiogenic and antitumor effects. However, the shortcoming with 2ME2 is that it is rapidly inactivated by 17β-hydroxysteroid dehydrogenase type 2. Thus a bis-sulphamoylated derivative of 2ME2, 2-Methoxyestradiol-bis-sulphamate (2MEBM) was synthesized in order to address the shortcoming of 2ME2. The aim of this in vitro study was to investigate the influence of 2MEBM on cell growth, morphology and tubulin structure in a cervical cancer (HeLa) cell line. Dose-dependent studies revealed that 0.55μM of 2MEBM inhibited cell growth by 50%. 2MEBM-treated cells showed an increase in the number of metaphase cells, apoptotic cells, and disrupted tubulin structure after 48 hours of exposure to 0.55μM of 2MEBM. Future studies will be conducted to further investigate the mechanism of action of 2MEBM in cervical carcinoma cells.Grants from the Cancer Association of South Africa (AK246), the Medical Research Council (AG374, AK076), National Research Foundation and Struwig Germishuysen Trust (AJ038).http://www.jstage.jst.go.jp/browse/biomedre

In vitro changes in mitochondrial potential, aggresome formation and caspase activity by a novel 17-beta-estradiol analog in mcf-7 breast adenocarcinoma cells

After a 24 hour exposure time, cells both apoptosis and autophagy were induced.This abstract was initially presented at the annual Biological Sciences Symposium, presented under the protection of the Suid-Afrikaanse Akademie vir Wetenskap en Kuns. The symposium was held at the University of Johannesburg on 01 October 2011.http://www.satnt.ac.z

Novel in silico-designed estradiol analogues are cytotoxic to a multidrug-resistant cell line at nanomolar concentrations

PURPOSE : 2-Methoxyestradiol (2ME) is a promising anticancer agent that disrupts the integrity and dynamics of the spindle network. In order to overcome the pharmacokinetic constraints of this compound, a panel of sulphamoylated estradiol analogues were in silico-designed by our laboratory. In this study, we analysed the potential of each analogue to induce cell death on a panel of cancer cell lines. Moreover, the mechanism of action of the most effective compounds was determined. METHODS : Cytotoxicity screening of the compounds and intermediates was performed on five different cancer cell lines to determine IG50 values. An in vitro tubulin polymerization assay was done to determine the effect of the drugs on tubulin polymerization while their intracellular effects on the microtubule network were assessed by immunofluorescence microscopy. RESULTS : IG50 calculations showed that the sulphamoylated analogues induce cytotoxicity at nanomolar concentrations in all cell lines, including the P-glycoprotein pump overexpressing multidrug-resistant uterine sarcoma cell line. The non-sulphamoylated compounds were only cytotoxic at micromolar ranges, if at all. The sulphamoylated compounds inhibited pure tubulin polymerization in a dose-dependent manner and induced microtubule destruction in cells after 24-h exposure. CONCLUSION : Results revealed that the novel sulphamoylated 2ME derivatives have potential as anti-cancer drugs, possibly even against chemoresistant cancer cells. These compounds disrupt the intracellular microtubule integrity which leads to mitotic block of the cells.The Research Development Programme of the University of Pretoria (RDP AOV840), the South African Medical Association (SAMA), the National Research Foundation (NRF Project # 86475, N00465, N00375, N00591), the Research Committee of the Faculty of Health Sciences, University of Pretoria (RESCOM), CANSA (AOV741, AOW228) and the Medical Research Council (MRC AOW110).http://link.springer.com/journal/2802016-02-28hb201