Fructose‐1,6‐bisphosphate induces generation of reactive oxygen species and activation of p53‐dependent cell death in human endometrial cancer cells
| Autor: | Krist Helen Antunes Fernandes, Marcella Tornquist Nassr, Bruna Pasqualotto Costa, Fernando Mendonça Diz, Leonardo Pfeiff Carlessi, Fernanda Bordignon Nunes, Gisele Branchini, Jarbas Rodrigues de Oliveira |
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| Rok vydání: | 2020 |
| Předmět: |
Programmed cell death
Fructose 1 6-bisphosphate Antineoplastic Agents Apoptosis Fructose 010501 environmental sciences Toxicology 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Downregulation and upregulation Cell Line Tumor Fructosediphosphates medicine Humans Cell Proliferation 030304 developmental biology 0105 earth and related environmental sciences chemistry.chemical_classification 0303 health sciences Reactive oxygen species Cell Death Chemistry Cell growth Endometrial cancer medicine.disease Endometrial Neoplasms Mitochondria Cell biology Cell culture Female Tumor Suppressor Protein p53 Reactive Oxygen Species |
| Zdroj: | Journal of Applied Toxicology. 41:1050-1062 |
| ISSN: | 1099-1263 0260-437X |
| DOI: | 10.1002/jat.4091 |
| Popis: | Fructose-1,6-bisphosphate (F1,6BP), an intermediate of the glycolytic pathway, has been found to play a promising anticancer effect; nevertheless, the mechanisms involved remain poorly understood. The present study aimed to evaluate the effect and mechanisms of F1,6BP in a human endometrial cancer cell line (Ishikawa). F1,6BP showed an antiproliferative and non-cytotoxic effect on endometrial cancer cells. These effects are related to the increase in reactive oxygen species (ROS) levels and mitochondrial membrane potential (ΔΨm). These harmful stimuli trigger the upregulation of the expression of pro-apoptotic genes (p53 and Bax), leading to the reduction of cell proliferation through inducing programmed cell death by apoptosis. Furthermore, F1,6BP-treated cells had the formation of autophagosomes induced, as well as a decrease in their proliferative capacity after withdrawing the treatment. Our results demonstrate that F1,6BP acts as an anticancer agent through the generation of mitochondrial instability, loss of cell function, and p53-dependent cell death. Thus, F1,6BP proves to be a potential molecule for use in the treatment against endometrial cancer. |
| Databáze: | OpenAIRE |
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