Cell death induced by Pteris semipinnata L. is associated with p53 and oxidant stress in gastric cancer cells.
In this study, we demonstrated that Ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) had stronger cytotoxicity against MKN-45, a gastric cancer cell line bearing wild-type p53 than MKN-28, another gastric cancer cell line containing missense mutation in p53. The rapid increase of ROS level was involved in the mechanism of cytotoxicity. Classical features of apoptosis induced by 5F were observed in MKN-45 cells only or more significant in MKN-45 cells than MKN-28 cells. Translocation of Bax from cytosol to mitochondria, reduction of delta psi m and DNA fragmentation were induced by 5F in the p53-dependent manner. We conclude that the expression of Bax and its downstream molecules requires the presentation of a wild-type p53 in the cells treated by 5F.
Liu
Zhimin
Z
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China.
Ng
Enders K W
EK
Liang
Nian-Ci
NC
Deng
Yi-Feng
YF
Leung
Billy C S
BC
Chen
George G
GG
D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D053938:DNA Fragmentation / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology; D004789:Enzyme Activation; D005420:Flavoproteins / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009336:Necrosis; D016877:Oxidants / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D032495:Pteris / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein
C479310:11-hydroxy-15-oxokaur-16-en-19-olic acid; C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; C494826:BAX protein, human; D004224:Diterpenes; D005420:Flavoproteins; D008565:Membrane Proteins; D016877:Oxidants; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione