title: Synergistic effect of ionizing radiation and beta-Lapachone against RKO human colon adenocarcinoma cells.
abstract: OBJECTIVE
  To reveal the interaction between beta-Lapachone (beta-lap) and ionizing radiation in causing cell death in RKO human colon adenocarcinoma cells, and to elucidate the potential usefulness of combined beta-lap treatment and radiotherapy for cancer treatment.
  
  
  METHODS
  The cytotoxicities of various treatments were determined in vitro using clonogenic and apoptotic cell death. The changes in cell cycle distribution were studied using flow cytometry and an in vitro kinase assay. The tumor growth was studied using RKO tumors grown s.c. in the hind leg BALB/c- nuslc nude mice.
  
  
  RESULTS
  beta-Lap caused clonogenic cell death and rapid apoptosis in RKO cells in vitro, in a dose dependent manner. The repair of sublethal radiation damage was almost completely inhibited when cells were maintained in beta-lap during the interval between the two-dose irradiation. Flow cytometry study demonstrated that beta-lap induced apoptosis, independent of the cell cycle phase, and completely prohibited the induction of radiation-induced G2 arrest in irradiated cells. The prohibition of radiation-induced G2 arrest is unclear, but may be related to the profound suppression of the p53, p21 and cyclin B1-Cdc2 kinase activities observed in cells treated with beta-lap. The combination of beta-lap and radiation markedly enhanced the radiation-induced growth suppression of tumors.
  
  
  CONCLUSIONS
  beta-Lap is cytotoxic against RKO cells, both in vitro and in vivo, and also sensitized cells to ionizing radiation by inhibiting sublethal radiation damage repair. beta-lap is potentially useful as a potent anti-cancer chemotherapy drug and potent radiosensitizer against cancer cells.
authors: Department of Microbiology, College of Medicine, Inha University, Incheon, Korea.
authors: Eun Jung
authors: EJ
authors: Kim
authors: In-Mi
authors: IM
authors: Ji
authors: Ki-Jung
authors: KJ
authors: Ahn
authors: Eun Kyung
authors: EK
authors: Choi
authors: Heon-Jin
authors: HJ
authors: Park
authors: Byung Uk
authors: BU
authors: Lim
authors: Chang W
authors: CW
authors: Song
authors: Heon Joo
authors: HJ
authors: Park