Thymidine phosphorylase suppresses apoptosis induced by microtubule-interfering agents

Hei Cheul Jeung, Xiao Fang Che, Misako Haraguchi, Tatsuhiko Furukawa, Chun Lei Zheng, Tomoyuki Sumizawa, Sun Young Rha, Kyung Roh Jae, Shin Ichi Akiyama

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Abstract

We investigated the ability of thymidine phosphorylase (TP) to confer cancer cells resistance to MIA (microtubule-interfering agents)-induced apoptosis. Jurkat cells were stably transfected with TP cDNA (Jurkat/TP) and the sensitivity to MIAs were examined. Jurkat/TP cells were more resistant to apoptosis induced by nocodazole, vincristine, vinblastine, paclitaxel and 2-methoxyestradiol than mock-trasfected Jurkat/CV cells. TP enzymatic activity was not required for this effect of TP. Jurkat/TP cells showed weak phosphorylation of Bcl-2, and kinase inhibitors staurosporine and genistein attenuated not only MIA-induced Bcl-2 phosphorylation but also cytotoxicity of MIA in Jurkat/CV, but not in Jurkat/TP. MIAs diminished expression of FasL in Jurkat/TP but not in Jurkat/CV, and neutralization of FasL by anti-FasL antibody considerably attenuated the cytotoxic effect of the MIAs in Jurkat/CV, but the effect of the antibody was marginal in Jurkat/TP cells. Our study provides further evidence that TP functions in conferring resistance on cancer cells to the stress induced by MIAs. In addition, we show that TP-induced inhibition of Bcl-2 phosphorylation and suppression of FasL may contribute to the protective function of TP in cancer cells.

Original languageEnglish
Pages (from-to)13-21
Number of pages9
JournalBiochemical Pharmacology
Volume70
Issue number1
DOIs
Publication statusPublished - 2005 Jul 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

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    Jeung, H. C., Che, X. F., Haraguchi, M., Furukawa, T., Zheng, C. L., Sumizawa, T., Rha, S. Y., Jae, K. R., & Akiyama, S. I. (2005). Thymidine phosphorylase suppresses apoptosis induced by microtubule-interfering agents. Biochemical Pharmacology, 70(1), 13-21. https://doi.org/10.1016/j.bcp.2005.04.017