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

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

A combination of an antimitotic and a bromodomain 4 inhibitor synergistically inhibits the metastatic MDA-MB-231 breast cancer cell line

CITATION: Mqoco, T., et al. 2019. A combination of an antimitotic and a bromodomain 4 inhibitor synergistically inhibits the metastatic MDA-MB-231 breast cancer cell line. BioMed Research International, 2019(1850462):1-13. doi:10.1155/2019/1850462The original publication is available at https://www.hindawi.com/journals/bmri/Current chemotherapeutic agents have many side effects and are toxic to normal cells, providing impetus to identify agents that can effectively eliminate tumorigenic cells without damaging healthy cells. The aim of this study was to examine whether combining a novel BRD4 inhibitor, ITH-47, with the antimitotic estradiol analogue, ESE-15-ol, would have a synergistic effect on inhibiting the growth of two different breast cancer cell lines in vitro. Our docking and molecular dynamics studies showed that compared to JQ1, ITH-47 showed a similar binding mode with hydrogen bonds forming between the ligand nitrogens of the pyrazole, ASN99, and water of the BRD4 protein. Data from cell growth studies revealed that the GI50 of ITH-47 and ESE-15-ol after 48 hours of exposure was determined to be 15 μM and 70 nM, respectively, in metastatic MDA-MB-231 breast cancer cells. In tumorigenic MCF-7 breast cancer cells, the GI50 of ITH-47 and ESE-15-ol was 75 μM and 60 nM, respectively, after 48 hours of exposure. Furthermore, the combination of 7.5 μM and 14 nM of ITH-47 and ESE-15-ol, respectively, resulted in 50% growth inhibition of MDA-MB-231 cells resulting in a synergistic combination index (CI) of 0.7. Flow cytometry studies revealed that, compared to the control, combination-treated MDA-MB-231 cells had significantly more cells present in the sub-G1 phase and the combination treatment induced apoptosis in the MDA-MB-231 cells. Compared to vehicle-treated cells, the combination-treated cells showed decreased levels of the BRD4, as well as c-Myc protein after 48 hours of exposure. In combination, the selective BRD4 inhibitor, ITH-47, and ESE-15-ol synergistically inhibited the growth of MDA-MB-231 breast cancer cells, but not of the MCF-7 cell line. This study provides evidence that resistance to BRD4 inhibitors may be overcome by combining inhibitors with other compounds, which may have treatment potential for hormone-independent breast cancers.NRF Thuthuka grantCancer Association of South AfricaMedical Research CouncilSchool of Medicine Research CommitteeStruwig Germeshuysen Trusthttps://www.hindawi.com/journals/bmri/2019/1850462/Publisher’s versio

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

Sulphamoylated estradiol analogue induces antiproliferative activity and apoptosis in breast cell lines

Research into potential anticancer agents has shown that 2-methoxyestradiol exerts antiproliferative activity in vitro and in vivo in an estrogen receptor-independent manner. Due to its limited biological accessibility and rapid metabolic degradation, several new analogues have been developed in recent years. This study investigated the in vitro effects of a novel in silicodesigned compound (C16) in an estrogen receptor-positive breast adenocarcinoma epithelial cell line (MCF-7), an estrogen receptor-negative breast adenocarcinoma epithelial cell line (MDA-MB-231) and a nontumorigenic breast cell line (MCF-12A). Light microscopy revealed decreased cell density, cells blocked in metaphase and the presence of apoptotic characteristics in all three cell lines after exposure to C16 for 24 h. Polarizationoptical transmitted light differential interference contrast revealed the presence of several rounded cells and decreased cell density. The xCELLigence real-time label-independent approach revealed that C16 exerted antiproliferative activity. Significant inhibition of cell growth was demonstrated after 24 h of exposure to 0.2 μM C16 in all three cell lines. However, the non-tumorigenic MCF-12A cell line recovered extremely well after 48 h when compared to the tumorigenic cell lines. This indicates that C16 acts as an antiproliferative agent, possesses antimitotic activity and induces apoptosis in vitro. These features warrant further investigation.The Cancer Association of South Africa (CANSA), the Struwig Germeshuysen Trust, RESCOM (Research Committee of the University of Pretoria), the National Research Foundation (NRF) and the Medical Research Council (MRC).http://www.springerlink.com/content/120185/http://www.cmbl.org.p

Differential cellular interaction of Sutherlandia frutescens extracts on tumorigenic and non-tumorigenic breast cells

Sutherlandia frutescens (SF) is a traditional Africanmedicinal aid employed for the treatment of various ailments such as inflammation, pulmonary asthma and congestion. The present study was conducted to demonstrate the differential cellular interaction of aqueous SF extracts in a breast adenocarcinoma epithelial cell line (MCF-7) and a non-tumorigenic breast cell line (MCF-12A) by means of polarization-optical differential interference contrast microscopy, crystal violet staining, light microscopy and flowcytometry. Results showed that aqueous SF extracts induced cell death inMCF-7 andMCF-12A via two types of cell death namely apoptosis and autophagy. Effects on proliferation and cytotoxicity were investigated by means of crystal violet staining. The latter indicated that, at a 1/10 dilution, the tumorigenic MCF-7 cell line was more prominently affected when compared to the nontumorigenic MCF-12A cell line. Apoptosis induction was demonstrated by qualitative and quantitative light microscopy and cell cycle progression studies, while autophagy induction was assessed by an increase inmicrotubule- associated protein light chain 3 (LC3) levels (a specific marker of autophagy). The MCF-7 tumorigenic cells, however, were more susceptible to these extracts when compared to the non-tumorigenic MCF-12A cells. Data obtained contribute towards understanding the differential cellular interaction exerted by aqueous SF extracts in tumorigenic versus non-tumorigenic breast cells. Results will enable researchers to further study cell death mechanisms induced by these aqueous extracts and to identify active compounds for evaluation in anticancer therapy and potential in vivo efficacy.Cancer Association of South Africa (Cape Town, South Africa)http://www.elsevier.com/locate/sajbhb201

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

Novel estradiol analogue induces apoptosis and autophagy in esophageal carcinoma cells

Cancer is the second leading cause of death in South Africa. The critical role that microtubules play in cell division makes them an ideal target for the development of chemotherapeutic drugs that prevent the hyperproliferation of cancer cells. The new in silico-designed estradiol analogue 2-ethyl-3-O-sulfamoyl-estra-1,3,5(10)16-tetraene (ESE-16) was investigated in terms of its in vitro antiproliferative effects on the esophageal carcinoma SNO cell line at a concentration of 0.18 μM and an exposure time of 24 h. Polarization-optical differential interference contrast and triple fluorescent staining (propidium iodide, Hoechst 33342 and acridine orange) revealed a decrease in cell density, metaphase arrest, and the occurrence of apoptotic bodies in the ESE-16-treated cells when compared to relevant controls. Treated cells also showed an increase in the presence of acidic vacuoles and lysosomes, suggesting the occurrence ofMedical Research Council of South Africa, the Cancer Association of South Africa, Research Committee of the University of Pretoria (RESCOM), the National Research Foundation (NRF),the Institute of Cellular and Molecular Medicine (ICMM), and the Struwig-Germeshuysen Cancer Research Trust of South Africa.http://link.springer.com/journal/11658hb201