Lipopolysaccharide prevents doxorubicin-induced apoptosis in RAW 264.7 macrophage cells by inhibiting p53 activation.
The effect of lipopolysaccharide on doxorubicin-induced cell death was studied by using mouse RAW 264.7 macrophage cells. Pretreatment with lipopolysaccharide at 10 ng/mL prevented doxorubicin-induced cell death and the inhibition was roughly dependent on the concentration of lipopolysaccharide. Posttreatment with lipopolysaccharide for 1 hour also prevented doxorubicin-induced cell death. Lipopolysaccharide inhibited DNA fragmentation and caspase-3 activation in doxorubicin-treated RAW 264.7 cells, suggesting the prevention of doxorubicin-induced apoptosis. Lipopolysaccharide did not significantly inhibit doxorubicin-induced DNA damage detected by single-cell gel electrophoresis (comet) assay. Lipopolysaccharide definitely inhibited the stabilization and nuclear translocation of p53 in doxorubicin-treated RAW 264.7 cells. Lipopolysaccharide, as well as being an inhibitor of p53, abolished doxorubicin-induced apoptosis. Therefore, p53 was suggested to play a pivotal role in the prevention of doxorubicin-induced apoptosis in RAW 264.7 cells by lipopolysaccharide.
Hassan
Ferdaus
F
Department of Microbiology and Immunology, School of Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
Islam
Shamima
S
Mu
Mya Mya
MM
Ito
Hiroyasu
H
Koide
Naoki
N
Mori
Isamu
I
Yoshida
Tomoaki
T
Yokochi
Takashi
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D004926:Escherichia coli; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects* / Q000502:physiology
D000903:Antibiotics, Antineoplastic; D008070:Lipopolysaccharides; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin