Tianshengyuan-1 (TSY-1) regulates cellular Telomerase activity by methylation of TERT promoter.
Oncotarget
; 8(5): 7977-7988, 2017 Jan 31.
Article
en En
| MEDLINE
| ID: mdl-28002788
Telomere and Telomerase have recently been explored as anti-aging and anti-cancer drug targets with only limited success. Previously we showed that the Chinese herbal medicine Tianshengyuan-1 (TSY-1), an agent used to treat bone marrow deficiency, has a profound effect on stimulating Telomerase activity in hematopoietic cells. Here, the mechanism of TSY-1 on cellular Telomerase activity was further investigated using HL60, a promyelocytic leukemia cell line, normal peripheral blood mononuclear cells, and CD34+ hematopoietic stem cells derived from umbilical cord blood. TSY-1 increases Telomerase activity in normal peripheral blood mononuclear cells and CD34+ hematopoietic stem cells with innately low Telomerase activity but decreases Telomerase activity in HL60 cells with high intrinsic Telomerase activity, both in a dose-response manner. Gene profiling analysis identified Telomerase reverse transcriptase (TERT) as the potential target gene associated with the TSY-1 effect, which was verified by both RT-PCR and western blot analysis. The ß-galactosidase reporter staining assay showed that the effect of TSY-1 on Telomerase activity correlates with cell senescence. TSY-1 induced hypomethylation within TERT core promoter in HL60 cells but induced hypermethylation within TERT core promoter in normal peripheral blood mononuclear cells and CD34+ hematopoietic stem cells. TSY-1 appears to affect the Telomerase activity in different cell lines differently and the effect is associated with TERT expression, possibly via the methylation of TERT promoter.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Madre Hematopoyéticas
/
Medicamentos Herbarios Chinos
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Leucocitos Mononucleares
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Leucemia Promielocítica Aguda
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Telómero
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Telomerasa
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Metilación de ADN
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Antineoplásicos Fitogénicos
Límite:
Humans
Idioma:
En
Revista:
Oncotarget
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos