title: The combined treatment of aspirin and radiation induces apoptosis by the regulation of bcl-2 and caspase-3 in human cervical cancer cell.
abstract: The antitumor mechanisms mediated by combined treatment of aspirin and radiation on human cervical cancer cells are unclear. In this paper, we studied whether aspirin and radiation induced apoptosis and whether the sensitivity to radiation was enhanced in aspirin-pretreated HeLa TG, human cervical cancer cells. We identified the regulation of apoptosis-responsive genes, bcl-2, caspase-3 and p53 after combined treatment. To investigate the growth inhibitory effect on HeLa TG cells after treatment of various nonsteroidal anti-inflammatory drugs (NSAIDs), we performed cell proliferation assay and colony-forming assay. In the presence of aspirin, sulindac and indomethacin, cell proliferation and colony formation were decreased in a time- and dose-dependent manner. According to flow cytometry analysis and Hoechst 33342 staining, we found that aspirin increased sub-G1 population and nuclear condensation of cervical cancer cells. Remarkably, the combined treatment decreased cell proliferation compared with treatment of 1 mM aspirin or 6 Gy radiation alone. Pretreatment of aspirin followed by irradiation also elevated the population of apoptotic cells. These results revealed that sensitivity to radiation was enhanced in aspirin-pretreated HeLa TG cells, and aspirin has the additive role for amplifying the radiotherapeutic effect in cervical cancer cells. Finally, combined treatment revealed bcl-2 repression and caspase-3 induction did not detect any change but p53 expression did. We have demonstrated that combined treatment of aspirin and radiation induces the antitumor effect mediated by bcl-2 and caspase-3 pathway in cervical cancer cells.
authors.affiliation: Department of Biomedical Sciences, National Institute of Health, Seoul 122-701, South Korea. anne8073@kebi.com
authors.forename: Kye Young
authors.initials: KY
authors.lastname: Kim
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Seol
authors.forename: Geong-A
authors.initials: GA
authors.lastname: Jeon
authors.forename: Myeong Jin
authors.initials: MJ
authors.lastname: Nam
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D001241:Aspirin / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000528:radiation effects; D019254:Genes, bcl-2; D016158:Genes, p53; D006367:HeLa Cells / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000502:physiology*; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013467:Sulindac / Q000494:pharmacology; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011838:Radiation-Sensitizing Agents; D016159:Tumor Suppressor Protein p53; D013467:Sulindac; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D001241:Aspirin; D007213:Indomethacin