Basal levels and patterns of anticancer drug-induced activation of nuclear factor-κB (NF-κB), and its attenuation by tamoxifen, dexamethasone, and curcumin in carcinoma cells

Shuang En Chuang, Pei Yen Yeh, Yen Shen Lu, Gi Ming Lai, Chao Ming Liao, Ming Gao, Ann Lii Cheng

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138 Citations (Scopus)

Abstract

Nuclear factor-κB (NF-κB) has been implicated in the development of drug resistance in cancer cells. We systematically examined the baseline levels of NF-κB activity of representative carcinoma cell lines, and the change of NF-κB activity in response to a challenge with four major anticancer drugs (doxorubicin, 5-fluorouracil, cisplatin, and paclitaxel). We found that the basal level of NF-κB activity was heterogeneous and roughly correlated with drug resistance. When challenged with various drugs, all the cell lines examined responded with a transient activation of NF-κB which then declined to basal level despite variation in the concentration of the agent and the timing of the treatment. In contrast to tumor necrosis factor-α (TNF-α), which activates NF-κB in minutes, NF-κB activation induced by anticancer drugs usually occurred more than 1hr after stimulation. A gradual increase of total NF-κB and its nuclear translocation, and cytoplasmic translocation of nuclear IκBα and its degradation were involved in this process. In particular, when cells were pretreated with common biologic modulators such as tamoxifen, dexamethasone, and curcumin, the doxorubicin-induced NF-κB activation was attenuated significantly. This inhibition may play a role in sensitizing cancer cells to chemotherapeutic drugs. This study has demonstrated that activation of NF-κB is a general cellular response to anticancer drugs, and the mechanism of activation appears to be distinct from that induced by TNF-α. These observations may have implications for improving the efficacy of systemic chemotherapy for cancer patients.

Original languageEnglish
Pages (from-to)1709-1716
Number of pages8
JournalBiochemical Pharmacology
Volume63
Issue number9
DOIs
Publication statusPublished - May 1 2002
Externally publishedYes

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Keywords

  • Curcumin
  • Drug resistance
  • NF-κB
  • Steroid
  • Tamoxifen
  • TPA

ASJC Scopus subject areas

  • Pharmacology

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