Cellular Levels of Thioredoxin Associated with Drug Sensitivity to Cisplatin, Mitomycin C, Doxorubicin, and Etoposide

Akira Yokomizo, Mayumi Ono, Yoshinari Makino, Takefumi Ohga, Morimasa Wada, Michihiko Kuwano, Kimitoshi Kohno, Hiroki Nanri, Takashi Okamoto, Junji Yodoi

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Abstract

Thioredoxin, a cellular thiol, functions as a self-defense mechanism in response to environmental stimuli, including oxidative stress. We first determined cellular levels of thioredoxin in several human bladder and prostatic cancer cell lines resistant to cfc-diamminedichloroplatinum(II) (cisplatin). All cisplatin-resistant cell lines had much higher levels of thioredoxin than those in their drug-sensitive parental counterpart We then, by introducing thioredoxin antisense expression plasmids into human bladder cancer T24 cells, established two bladder cancer cell lines that had decreased levels of thioredoxin. These thioredoxin antisense transfectants showed increased sensitivity to cisplatin and also to other superoxide-generating agents, i.e., doxorubicin, mitomycin C, etoposide, and hydrogen peroxide, as well as to UV irradiation, but not to the tubulin-targeting agents, vincristine, and colchicine. Cellular levels of thioredoxin thus appear to limit sensitivity to various superoxide-generating anticancer drugs in cancer cells.

Original languageEnglish
Pages (from-to)4293-4296
Number of pages4
JournalCancer Research
Volume55
Issue number19
Publication statusPublished - Oct 1 1995

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Yokomizo, A., Ono, M., Makino, Y., Ohga, T., Wada, M., Kuwano, M., ... Yodoi, J. (1995). Cellular Levels of Thioredoxin Associated with Drug Sensitivity to Cisplatin, Mitomycin C, Doxorubicin, and Etoposide. Cancer Research, 55(19), 4293-4296.