title: Oridonin induces apoptosis through the mitochondrial pathway in human gastric cancer SGC-7901 cells.
abstract: Oridonin is one of the most important antitumor active ingredients of Rabdosia rubescens. Recently published studies from our laboratory have demonstrated that oridonin was able to arrest human gastric cancer SGC-7901 cells at G2/M phase. However, little is known about inducing apoptosis in gastric cancer. The aim of this study was to investigate the effect of oridonin on antineoplastic capability of SGC-7901 cells and the detailed molecular mechanism of oridonin-mediated intrinsic pathway of apoptosis. Cell proliferation was assessed by MTT assay while apoptosis induced by oridonin was determined by Hoechst 33342 staining assay and Annexin V/PI double staining assay. Early apoptotic rate was stained by Annexin V/PI and detected by flow cytometry. Apoptosis pathway was analyzed by western blot analysis of Bcl-2, Bax, cytochrome c and caspase-3 expression. The results showed that oridonin was able to inhibit the SGC-7901 cell proliferation, the 50% growth inhibition (IC50) was 22.74 µM. Oridonin could induce cell apoptosis of SGC-7901 cells and the early apoptotic rates induced by 0, 20, 40, 80 µmol/l oridonin were 1.53±0.67, 3.33±0.29, 84.80±0.82 and 96.43±0.51%, respectively. Western blot analysis revealed that oridonin downregulated Bcl-2 protein (the anti-apoptotic factor) and upregulated Bax protein (pro-apoptotic factor), eventually leading to a reduction in the ratio of Bcl-2/Bax proteins. Furthermore, oridonin induced the release of cytochrome c from the mitochondria to the cytosol and the activation of caspase-3. Taken together, the current study suggested that oridonin induced apoptosis in SGC-7901 cells via the mitochondrial signal pathway, which may represent one of the major mechanisms of oridonin-mediated apoptosis in SGC-7901 cells.
authors.affiliation: The Institute of Materia Medica, The Research Center of Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, P.R. China.
authors.forename: Shiyong
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Pharmacy, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, P.R. China.
authors.forename: Huixin
authors.initials: H
authors.lastname: Tan
authors.affiliation: Engineering Research Center of Natural Anticancer Drugs of Ministry of Education, Harbin University of Commerce, Harbin 150076, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhu
authors.affiliation: The Institute of Materia Medica, The Research Center of Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, P.R. China.
authors.forename: Haiyu
authors.initials: H
authors.lastname: Gao
authors.affiliation: The Institute of Materia Medica, The Research Center of Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, P.R. China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Lv
authors.affiliation: The Institute of Materia Medica, The Research Center of Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gang
authors.affiliation: The Institute of Materia Medica, The Research Center of Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, P.R. China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Ji
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C000595707:BCL2 protein, human; D045786:Diterpenes, Kaurane; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C011959:oridonin; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3