title: The combination effect of sodium butyrate and 5-Aza-2'-deoxycytidine on radiosensitivity in RKO colorectal cancer and MCF-7 breast cancer cell lines.
abstract: BACKGROUND
  The overall level of chromatin compaction is an important mechanism of radiosensitivity, and modification of DNA methylation and histone deacetylation may increase radiosensitivity by altering chromatin compaction. In this study, we investigated the effect of a demethylating agent, a histone deacetylase(HDAC) inhibitor, and the two agents combined on radiosensitivity in human colon and breast cancer cell lines.
  
  
  METHODS
  In this study, we used RKO colorectal cancer cell line and MCF-7 breast cancer cell lines and normal colon cell lines. On each of the cell lines, we used three different agents: the HDAC inhibitor sodium butyrate(SB), the demethylating agent 5-Aza-2'-deoxycytidine(5-aza-DC), and radiation. We then estimated the percentage of the cell survival using the XTT method and experimented to determine if there was an augmentation in the therapeutic effect by using different combinations of the two or three of the treatment methods.
  
  
  RESULTS
  After treatment of each cell lines with 5-aza-DC, SB and 6 grays of radiation, we observed that the survival fraction was lower after the treatment with 5-aza-DC or SB than with radiation alone in RKO and MCF-7 cell lines(p < 0.001). The survival fraction was lowest when the two agents, 5-aza-DC and SB were combined with radiation in both RKO and MCF-cell lines.
  
  
  CONCLUSIONS
  In conclusion, 5-aza-DC and SB can enhance radiosensitivity in both MCF-7 and RKO cell lines. The combination effect of a demethylating agent and an HDAC inhibitor is more effective than that of single agent treatment in both breast and colon cancer cell lines.
authors.affiliation: Department of Surgery, Uijongbu St Mary's Hospital, College of Medicine, The Catholic University of Korea, South Korea. surgeryman@catholic.ac.kr
authors.forename: Hang Joo
authors.initials: HJ
authors.lastname: Cho
authors.forename: Sin Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Kee Hwan
authors.initials: KH
authors.lastname: Kim
authors.forename: Won Kyung
authors.initials: WK
authors.lastname: Kang
authors.forename: Ji Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Seong Tack
authors.initials: ST
authors.lastname: Oh
authors.forename: Jeong Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Chang Hyeok
authors.initials: CH
authors.lastname: An
mesh_terms: D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001943:Breast Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D002087:Butyrates / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D019175:DNA Methylation; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
chemical_list: D002087:Butyrates; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D011838:Radiation-Sensitizing Agents; D000077209:Decitabine; D001374:Azacitidine