Magnolol induces apoptosis via activation of both mitochondrial and death receptor pathways in A375-S2 cells.
Magnolol inhibited proliferation of human malignant melanoma A375-S2 cells. The drug induced oligonucleosomal fragmentation of DNA in A375-S2 cells and increased caspase-3, 8, 9 activities followed by the degradation of caspase-3 substrates, inhibitor of caspase dependent DNase (ICAD) and poly-(ADP-ribose) polymerase (PARP). Pan-caspase inhibitor (z-VADfmk), caspase-3 inhibitor (z-DEVD-fmk), capase-8 inhibitor (z-IETD-fmk), caspase-9 inhibitor (z-LEHD-fmk) and caspase-10 inhibitor (z-AEVD-fmk) inhibited magnolol-induced A375-S2 cell apoptosis. The level of anti-apoptotic mitochondrial protein Bcl-2 was up-regulated while the level of pro-apoptotic protein Bax was down-regulated. Taken together, our results indicate that magnolol induces apoptosis by activation of both mitochondrial and death receptor pathways in A375-S2 cells.
You
Qingjun
Q
Department of Cardiothoracic Surgery, Wuxi The Forth Hospital, Wuxi City Huihe Road 200, 214062, Wuxi, China.
Li
Mingqiu
M
Jiao
Guoqing
G
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D006690:Bisbenzimidazole; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000737:chemistry / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D053218:Receptors, Death Domain / Q000819:agonists*; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000502:physiology; D019014:fas Receptor / Q000276:immunology
D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D004396:Coloring Agents; D004273:DNA, Neoplasm; D017705:Lignans; D019253:Proto-Oncogene Proteins c-bcl-2; D053218:Receptors, Death Domain; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; C005498:magnolol; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D006690:Bisbenzimidazole