Dysregulation of Catalase by a Sulphamoylated Estradiol Analogue Culminates in Antimitotic Activity and Cell Death Induction in Breast Cancer Cell Lines.
Maphuti T LebeloAnnie Margaretha JoubertMichelle Helen VisagiePublished in: Molecules (Basel, Switzerland) (2021)
Recent findings revealed that 2-ethyl-17-oxoestra-1,3,5(10)-trien-3-yl sulfamate (ESE-one) induces antiproliferative activity and cell rounding dependent on the generation of superoxide anion, hydrogen peroxide and peroxyl radical. In the current study, the role of these reactive oxygen species was assessed in the activity exerted by ESE-one on cell cycle progression, mitochondrial membrane potential and cell death induction in breast tumorigenic cells. The influence of ESE-one was also investigated on superoxide dismutase and catalase activity. ESE-one induced a time-dependent accumulation of cells in the G1 phase and G2/M phase that is partially impaired by tiron and trolox and N,N'-dimethylthiourea suggesting that superoxide anion, hydrogen peroxide and peroxyl radical are required for these effects exerted by ESE-one. Flow cytometry data in MCF-7 cells demonstrated that tiron decreased depolarization of the membrane potential in ESE-one exposed cells, indicating that superoxide anion plays a role in the depolarization effects induced by ESE-one. Spectrophotometry data showed that ESE-one decreased catalase activity in both cell lines. This study contributes towards pertinent information regarding the effects of an in silico-designed sulfamoylated compound on antioxidant enzymes leading to aberrant quantities of specific reactive oxygen species resulting in antimitotic activity culminating in the induction of cell death in breast cancer cell lines.
Keyphrases
- hydrogen peroxide
- cell death
- cell cycle arrest
- induced apoptosis
- cell cycle
- reactive oxygen species
- nitric oxide
- oxidative stress
- flow cytometry
- cell proliferation
- endoplasmic reticulum stress
- risk assessment
- healthcare
- big data
- signaling pathway
- deep learning
- climate change
- anti inflammatory
- machine learning
- molecular docking