ZGDHu-1-inducing apoptosis of SHI-1 leukemia cells and its molecular mechanism / 中国实验血液学杂志
Journal of Experimental Hematology
; (6): 483-489, 2007.
Article
in Chinese
| WPRIM (Western Pacific)
| ID: wpr-230239
Responsible library:
WPRO
ABSTRACT
The aim of study was to investigate the mechanism of N, N'-di-(m-methylphenyl)-3, 6-dimethyl-1, 4-dihydro-1, 2, 4, 5-tetrazine-1, 4-dicarboamide (ZGDHu-1) inducing apoptosis in SHI-1 human leukemia cell line. Different concentrations of ZGDHu-1 and different times of culture were used to treat SHI-1 cells; the apoptosis of SHI-1 cells was analyzed by morphology, DNA agarose gel electrophoresis, DNA content detection, Annexin-V/PI and Hoechst33258 labeling method, the mitochondrial transmembrane potential (Delta Psi m) were measured by dihydrorhodamin 123, and expressions of bcl-2, bax, Fas, p53 and mitochondrial membrane protein were analyzed by flow cytometry, while the bcl-2, bax and p53 gene were analyzed by RT-PCR. The transcriptional level of hTERT-mRNA was measured by real-time fluorescence quantitative RT-PCR. The results showed that after exposure to ZGDHu-1, SHI-1 cells were induced to apoptosis in a time-and does-dependent manner. SHI-1 cell apoptosis was confirmed by typical cell morphology, DNA fragmentation, sub-G(1) phase, Hoechst33258 and Annexin-V/PI labeling etc. The expression of bax, bax/bcl-2, p53 and Fas gene significantly increased and bcl-2 slightly decreased. ZGDHu-1 could increased the expression of mitochondrial membrane protein in a dose-dependent manner while Delta Psi m reduced. The expression of hTERT-mRNA significantly decreased. It is concluded that ZGDHu-1 can up-regulate the expression of p53, bax and bax/bcl-2. The mitochondrial pathway mediated by descent of mitochondrial transmembrane potential may be one of the mechanisms inducing apoptosis by ZGDHu-1, in which Fas gene also participates. Telomerase may be an effective gene target for anti-tumour effect of ZGDHu-1.
Full text:
Available
Health context:
SDG3 - Target 3.4 Reduce premature mortality due to noncommunicable diseases
Health problem:
Leukemia
Database:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Pharmacology
/
RNA, Messenger
/
Leukemia, Monocytic, Acute
/
Tumor Suppressor Protein p53
/
Apoptosis
/
Telomerase
/
Proto-Oncogene Proteins c-bcl-2
/
Cell Line, Tumor
/
Dose-Response Relationship, Drug
Limits:
Animals
/
Humans
Language:
Chinese
Journal:
Journal of Experimental Hematology
Year:
2007
Document type:
Article