ZM-66, a new podophyllotoxin derivative inhibits proliferation and induces apoptosis in K562/ADM cells / 中国医学科学杂志(英文版)
Chinese Medical Sciences Journal
; (4): 174-179, 2014.
Article
in English
| WPRIM (Western Pacific)
| ID: wpr-242875
Responsible library:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the anti-tumor effect of ZM-66 on multidrug-resistant leukemic cell line K562/ADM.</p><p><b>METHODS</b>The K562/ADM cells were treated with varying concentrations (0, 1, 2, 4 × 10⁻³ mmol/L) of ZM-66 or etoposide for 24 hours. The proliferation was detected by Sulforhodamine B Sodium Salt (SRB) assay and apoptosis was detected by flow cytometry analysis and fluorescent staining. In addition, the expression levels of p53 and bax genes in K562/ADM cells were detected by RT-PCR analysis. The level of P-glycoprotein (P-gp), P53 and Bax protein in K562/ADM cells were detected by Western blot assay.</p><p><b>RESULTS</b>SRB assay demonstrated that etoposide had little inhibitory effect on K562/ADM cells, whereas ZM-66 (1, 2, 4 × 10⁻³ mmol/L) had significantly inhibitory effect on K562/ADM cells (all P<0.01). The acridine orange/propidium iodide dual staining showed that there were typical condensation of chromatin and nuclear fragmentation nuclei with red color in ZM-66 treated cells. Flow cytometric analysis showed that there was a significantly increase of apoptotic cells in K562/ADM cells after treated with ZM-66. RT-PCR showed that the p53 and bax mRNA expression levels in K562/ADM cells treated with ZM-66 at 1, 2, 4 × 10⁻³ mmol/L were higher than those in the cell without treatment. Western blot showed that the P53 and Bax protein expression levels in K562/ADM cells treated with ZM-66 at 2, 4 × 10⁻³ mmol/L were higher than those in the cell without treatment. But the P-gp protein expression level in K562/ADM cells treated with ZM-66 at 2, 4 × 10⁻³ mmol/L was gradually lower than those in the cell without treatment.</p><p><b>CONCLUSION</b>ZM-66 is able to induce cell death by apoptosis in vitro, as a result of the reverse of the apoptosis resistance in drug-resistant K562/ADM cells by modulating expression of key factors associated with apoptosis induction.</p>
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Podophyllotoxin
/
RNA, Messenger
/
Chemistry
/
Blotting, Western
/
Apoptosis
/
K562 Cells
/
Cell Proliferation
/
Flow Cytometry
/
Genetics
Limits:
Humans
Language:
English
Journal:
Chinese Medical Sciences Journal
Year:
2014
Document type:
Article