The investigation of resveratrol and analogs as potential inducers of fetal hemoglobin
| Autor: | Marios Phylactides, Swee Lay Thein, Luca Forti, Andria Theodorou, Maria Rita Cramarossa, Roberto Gambari, Pantelis Spyrou, Marina Kleanthous |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Ineffective erythropoiesis congenital hereditary and neonatal diseases and abnormalities Cell Survival Cells Resveratrol Biology medicine.disease_cause Beta-thalassemia Antioxidants NO 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine hemic and lymphatic diseases Fetal hemoglobin Stilbenes medicine Humans Globin Cytotoxicity Molecular Biology Cells Cultured chemistry.chemical_classification Antioxidant Erythroid Precursor Cells Fetal Hemoglobin K562 Cells Molecular Medicine Hematology Cell Biology Reactive oxygen species Cultured Phytoalexin medicine.disease 3. Good health 030104 developmental biology Hemoglobinopathy Biochemistry chemistry 030220 oncology & carcinogenesis |
| Popis: | Βeta-thalassemia, is a hemoglobinopathy characterized by reduced beta-globin chain synthesis, leading to imbalanced globin chain production, ineffective erythropoiesis and anemia. Increasing gamma-globin gene expression is a promising therapeutic approach as it reduces this imbalance by combining with the excess alpha globin chains and producing fetal hemoglobin (HbF). Furthermore, increased iron absorption and repeated blood transfusions lead to iron overload and tissue damage secondary to reactive oxygen species. Compounds exhibiting both antioxidant and HbF inducing activities are, therefore, highly desirable therapeutic agents. Resveratrol, a natural phytoalexin, combines these two activities but is also cytotoxic. Nine hydroxystilbenic resveratrol derivatives were synthesized in an attempt to identify compounds that retain the HbF-inducing and antioxidant activities of resveratrol but exhibit reduced cytotoxicity. Three derivatives (P1, P4 and P11) exhibited similar hemoglobin-inducing properties to resveratrol in K562 cells, however, only P11 showed reduced cytotoxicity. All three derivatives demonstrated variable HbF-inducing activity in primary erythroid progenitor cells from healthy donors. Resveratrol and P11 increased HbF induction significantly, with P11 having the highest activity. Additionally, P4 significantly increased progenitor numbers. A combinatorial treatment in K562 cells using resveratrol and decitabine resulted in a statistically significant increase in hemoglobin-inducing activity only above the level shown by resveratrol alone. |
| Databáze: | OpenAIRE |
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