Arsenic trioxide overcomes apoptosis inhibition in K562/ADM cells by regulating vital components in apoptotic pathway.
Extensive researches have revealed that arsenical can exert anti-tumor efficacy against several kinds of cancers including leukemia. Though, little is known about the effects of arsenical on leukemia resistant to chemotherapy, emerging as a serious clinical problem. In this study, we tested arsenic trioxide (As(2)O(3))-induced apoptosis in K562/ADM multidrug-resistant leukemic cells and investigated its possible mechanisms. Using microscopy, flow cytometry (FCM) and DNA electrophoresis, we found that As(2)O(3) could induce the cells to undergo G2/M phase arrest and apoptosis. Further, it was shown that the levels of FAS and P53 proteins increased and P-glycoprotein (P-gp) decreased upon drug action by employing FCM. Reverse transcription polymerase chain reaction (RT-PCR) detected increased mRNA product of FAS and caspase-3 genes and reduced MDR1 mRNA. CASPASE-3 activity was also enhanced after As(2)O(3) treatment. However, the expression of BCL-2 protein was not affected by the drug. Taken together, As(2)O(3) is able to reverse the apoptosis resistance in drug-resistant K562/ADM cells by modulating expression or activity of key factors associated with apoptosis induction.
Wang
Dong-Hai
DH
Molecular Cell Biology Research Center, Key Laboratory of Preclinical Study for Drugs of Gansu Province, Lanzhou University School of Medicine, Lanzhou 730000, PR China.
Wei
Hu-Lai
HL
Zhao
Huai-Shun
HS
Hao
Chun-Yan
CY
Min
Zhi-Hui
ZH
Liu
Jian-Min
JM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D019450:Genes, MDR; D006801:Humans; D020014:K562 Cells / Q000187:drug effects*; D010087:Oxides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000077237:Arsenic Trioxide