Thymidine phosphorylase suppresses apoptosis induced by microtubule-interfering agents

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

Research output: Contribution to journalArticle

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

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Thymidine Phosphorylase
Microtubules
Apoptosis
Phosphorylation
Jurkat Cells
Cells
Nocodazole
Neoplasms
Staurosporine
Vinblastine
Antibodies
Genistein
Vincristine
Cytotoxicity
Paclitaxel

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

Jeung, H. C., Che, X. F., Haraguchi, M., Furukawa, T., Zheng, C. L., Sumizawa, T., ... 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
Jeung, Hei Cheul ; Che, Xiao Fang ; Haraguchi, Misako ; Furukawa, Tatsuhiko ; Zheng, Chun Lei ; Sumizawa, Tomoyuki ; Rha, SunYoung ; Jae, Kyung Roh ; Akiyama, Shin Ichi. / Thymidine phosphorylase suppresses apoptosis induced by microtubule-interfering agents. In: Biochemical Pharmacology. 2005 ; Vol. 70, No. 1. pp. 13-21.
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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.",
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Jeung, HC, Che, XF, Haraguchi, M, Furukawa, T, Zheng, CL, Sumizawa, T, Rha, S, Jae, KR & Akiyama, SI 2005, 'Thymidine phosphorylase suppresses apoptosis induced by microtubule-interfering agents', Biochemical Pharmacology, vol. 70, no. 1, pp. 13-21. https://doi.org/10.1016/j.bcp.2005.04.017

Thymidine phosphorylase suppresses apoptosis induced by microtubule-interfering agents. / Jeung, Hei Cheul; Che, Xiao Fang; Haraguchi, Misako; Furukawa, Tatsuhiko; Zheng, Chun Lei; Sumizawa, Tomoyuki; Rha, SunYoung; Jae, Kyung Roh; Akiyama, Shin Ichi.

In: Biochemical Pharmacology, Vol. 70, No. 1, 01.07.2005, p. 13-21.

Research output: Contribution to journalArticle

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AU - Jeung, Hei Cheul

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AU - Zheng, Chun Lei

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AU - Akiyama, Shin Ichi

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