Article Publish Status: FREE
Abstract Title:

Tanshinone IIA enhances bystander cell killing of cancer cells expressing Drosophila melanogaster deoxyribonucleoside kinase in nuclei and mitochondria.

Abstract Source:

Oncol Rep. 2015 Sep ;34(3):1487-93. Epub 2015 Jul 2. PMID: 26134602

Abstract Author(s):

Haiyang Jiang, Lei Zhao, Xiaoshen Dong, Anning He, Caiwei Zheng, Magnus Johansson, Anna Karlsson, Xinyu Zheng

Article Affiliation:

Haiyang Jiang


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 linewas 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 Chinesemedicine 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 killingwere 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.

Study Type : Insect Study
Additional Links
Pharmacological Actions : Chemotherapeutic : CK(2328) : AC(1086)

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