Ardipusilloside I purified from Ardisia pusilla competitively binds VEGFR and induces apoptosis in NCI-H460 cells.
The present study was to evaluate the effects of Ardipusilloside I isolated from Ardisia pusilla on the growth, vascular endothelial growth factor receptor (VEGFR) expression and apoptosis of NCI-H460 cell line by MTT, ELISA and flow cytometer, respectively. The docking assay between Ardipusilloside I and VEGFR was studied by Sybyl/Sketch module. The change of microstructure was observed by transmission electron microscope (TEM). DNA fragmentation was visualized by agarose gel electrophoresis. The protein expression of Bax and Bcl-2 was detected by immunohistochemistry (IHC). A series of changes were observed in NCI-H460 cell treated by Ardipusilloside I, including microstructure, DNA fragmentation, protein expression of VEGFR, Bax and Bcl-2. The results showed Ardipusilloside I had a good docking with VEGFR and could inhibit growth and induce apoptosis of NCI-H460 cell in a dose-dependent manner. Cell cycle was significantly stopped at the G(1) phase. Under electronic microscope, the morphology of NCI-H460 cell treated with Ardipusilloside I showed nuclear karyopycnosis, chromatin agglutination and typical apoptotic body. VEGFR and Bcl-2 expression were decreased and Bax expression was increased. In conclusion, all these results demonstrate that Ardipusilloside I has a good docking with VEGFR and has an inhibitory effect on growth of NCI-H460 cell and can induce its apoptosis.
Zhang
Yanmin
Y
School of Medicine, Xi'an Jiaotong University, Xi'an 710061, PR China.
Qu
Youle
Y
Zhang
Jie
J
Wang
Xiaojuan
X
D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D031644:Ardisia / Q000737:chemistry*; D001667:Binding, Competitive / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D053960:DNA Breaks / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D012503:Saponins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; D051028:bcl-2-Associated X Protein; C087799:ardipusilloside I; D009828:Oleanolic Acid; D040262:Receptors, Vascular Endothelial Growth Factor