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

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

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

Bibliographical note

Funding Information:
We thank Ms. Sudo, E. for her excellent technical assistance and we are also grateful to Ms. Kakura, H. for her sincere secretarial assistance. This work was supported in part by grants-in-aid for a postdoctoral fellowship for Asian researchers from the Tokyo Biochemical Research Foundation.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

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