title: Daidzein induced apoptosis via down-regulation of Bcl-2/Bax and triggering of the mitochondrial pathway in BGC-823 cells.
abstract: Daidzein belongs to the group of isoflavones, found in a wide variety of plant-derived foods, especially in soybeans and soy-based foods. In this study, the effect of daidzein on human gastric carcinoma cells (BGC-823) and its mechanism were investigated. MTT assay was applied in the detection of the inhibitory effects of daidzein on cell proliferation. Hoechst-propidium iodide staining and flow cytometry were used to examine the apoptosis as well as the mitochondrial transmembrane potential. Western blotting was performed to detect the expression of apoptosis-associated proteins: cleaved PARP, cleaved caspase-9, cleaved caspase-3, Bcl-2, and Bax. Daidzein significantly inhibited the growth and proliferation of human gastric carcinoma cells (BGC-823) in a concentration- and time-dependent manner. Furthermore, it was found that an insult of daidzein to BGC-823 cells caused them to die by disruption of mitochondrial transmembrane potential, demonstrated not only by staining dead cells for phosphatidylserine but also by the up-regulation (cleaved PARP, cleaved caspase-9, cleaved caspase-3, Bax) and down-regulation (Bcl-2) of proteins associated with apoptosis and survival; whereas, the pan-caspase inhibitor z-VAD-fmk could partially rescue cells against damage of daidzein. Taken together, the results of this study demonstrate that daidzein significantly induces apoptosis via a mitochondrial pathway. Specifically, daidzein induced a change in the Bax/Bcl-2 ratios and activation of caspases-3 and -9 and the cleavage of PARP. Therefore, daidzein has the potential for use as a therapeutic agent for the treatment of gastric carcinoma.
authors.affiliation: Department of Emergency Surgery, First Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, Heilongjiang, China.
authors.forename: Shuyao
authors.initials: S
authors.lastname: Tang
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Meng
authors.forename: Xuesong
authors.initials: X
authors.lastname: Dong
authors.forename: Kaifu
authors.initials: K
authors.lastname: Wang
authors.forename: Yuebin
authors.initials: Y
authors.lastname: Qi
authors.forename: Chao
authors.initials: C
authors.lastname: Chu
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Limin
authors.initials: L
authors.lastname: Hou
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D048789:Phytoestrogens / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C494826:BAX protein, human; D007529:Isoflavones; D048789:Phytoestrogens; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C004742:daidzein; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9