TY - JOUR AB - Heterologous expression of the Drosophila melanogaster multi-substrate deoxyribonucleoside kinase (Dm-dNK) increases the sensitivity of cancer cells to several cytotoxic nucleoside analogs. Thus, it may be used as a suicide gene in combined gene/chemotherapy treatment of cancer. To further characterize this potential suicide gene, we constructed two retroviral vectors that enabled the expression of Dm-dNK in cancer cells. One vector harbored the wild‑type enzyme that localized to the nucleus. The other vector harbored a mitochondrial localized mutant enzyme that was constructed by deleting the nuclear localization signal and fusing it to a mitochondrial import signal of cytochrome c oxidase. A thymidine kinase-deficient osteosarcoma cell line was transduced with the recombinant viruses. The sensitivity and bystander cell killing in the presence of pyrimidine nucleoside analogs (E)-5-(2-bromovinyl)‑2'‑deoxyuridine and 1-β-D-arabinofuranosylthymine were investigated. Tanshinone IIA is a constituent of Danshen; a traditional Chinese medicine used in the treatment of cardiovascular diseases. This study also looked at the influence of Tanshinone IIA on the bystander effect and the underlying mechanisms. We showed that sensitivity of the osteosarcoma cell line to the nucleoside analogs and the efficiency of bystander cell killing were independent of the subcellular localization of Dm-dNK. The enhanced effect of tanshinone IIA on the bystander effect was related to the increased expression of Cx43 and Cx26. AD - Department of Breast Surgery, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, P.R. China Center of Experiment Technology and Medical Research, China Medical University, Shenyang, Liaoning, P.R. China Laboratory 1, Cancer Institute, China Medical University, Shenyang, Liaoning, P.R. China Brandeis University, Waltham, MA, USA Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden AU - Jiang,Haiyang AU - Zhao,Lei AU - Dong,Xiaoshen AU - He,Anning AU - Zheng,Caiwei AU - Johansson,Magnus AU - Karlsson,Anna AU - Zheng,Xinyu DA - 2015/09/01 DO - 10.3892/or.2015.4102 EP - 1493 IS - 3 JO - Oncol Rep KW - tanshinone IIA nucleoside kinase nucleoside analog bystander effect suicide gene PY - 2015 SN - 1021-335X 1791-2431 SP - 1487 ST - Tanshinone IIA enhances bystander cell killing of cancer cells expressing Drosophila melanogaster deoxyribonucleoside kinase in nuclei and mitochondria T2 - Oncology Reports TI - Tanshinone IIA enhances bystander cell killing of cancer cells expressing Drosophila melanogaster deoxyribonucleoside kinase in nuclei and mitochondria UR - https://doi.org/10.3892/or.2015.4102 VL - 34 ER -