Phenoxazine derivatives induce caspase-independent cell death in human glioblastoma cell lines, A-172 and U-251 MG.
The apoptotic effects of 2-amino-4,4alpha-dihydro-4alpha, 7-dimethyl-3H-phenoxazine-3-one (Phx-1) and 2-aminophenoxazine-3-one (Phx-3) on human glioblastoma cell lines, A-172 and U-251 MG were studied. These phenoxazines extensively decreased the viability of A-172 and U-251 MG cells (IC50 of Phx-1: 60 microM, in both lines; IC50 of Phx-3: 10 and 3 microM, for A-172 and U-251 cells, respectively). Phx-1 and Phx-3 increased the population of annexin V and PI double-positive cells in A-172 and U-251 MG cells, resulting in cell death at late stage apoptosis/necrosis. The activities of caspase-3/7 were greatly increased in A-172 and U-251 MG cells treated with Phx-1 or Phx-3. However, a pan-caspase inhibitor, z-VAD-fmk, failed to reverse the antiproliferative and apoptotic effects of Phx-1 and Phx-3 in both cell lines. In conclusion, Phx-1 and Phx-3 exert significant anti-cancer effects against human glioblastoma cell lines, A-172 and U-251 MG, mediated by the caspase-independent apoptotic cell death pathway.
Shirato
Ken
K
Laboratory of Physiological Sciences, Faculty of Human Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192, Japan.
Imaizumi
Kazuhiko
K
Abe
Akihisa
A
Tomoda
Akio
A
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D010078:Oxazines / Q000494:pharmacology*
C104202:2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one; D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D010078:Oxazines; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C005512:3-aminophenoxazone; D020169:Caspases