Regulative function of extracellular regulated protein kinases and telomerase in apoptosis of hepatocarcinomatous and leukemic cell lines.
In order to investigate the change of telomerase activity and phosphorylated (activated) extracellular regulated protein kinases (ERK) 1 and 2 in hepatocarcinomatous cell line SMMC7721 and leukemic cell line K562 proliferation inhibition and apoptosis, three kinds of chemotherapeutic drugs harringtonine (HRT), vincristine (VCR) and etoposide (VP-16) were selected as inducers; and MTT assay, flow cytometry analysis, telomeric repeat amplification protocol (TRAP) assay and bioluminescence analysis were used. The results showed that after treatment of HRT, VCR and VP-16 for 24 hours, the cell proliferation was inhibited, apoptosis was induced, and telomerase activity and the protein expression of phosphorylated ERK1/2 were down-regulated. In HRT treated groups, the descendent grade was the most obvious. It was concluded that the common molecular mechanism of these chemotherapeutic drugs killing SMMC7721 and K562 cell lines might be through inhibiting ERK signal transduction pathways, cutting down ERK activity, reducing the transcription of target genes of ERKs, then indirectly down-regulate telomerase activity, and cell apoptosis is the final result of durative loss of telomere.
Li
Deng-Ju
DJ
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. lidengju@163.net
Zhang
Yao-Zhen
YZ
Meng
Fan-Kai
FK
Zhang
Dong-Hua
DH
Liu
Wen-Li
WL
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000201:enzymology* / Q000473:pathology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D019098:Telomerase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D019098:Telomerase