Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NFκB transcription factors

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Abstract

Malignant gliomas are a debilitating class of brain tumors that are resistant to radiation and chemotherapeutic drugs, contributing to the poor prognosis associated with these tumors. Over-expression of transcription factors such as NFκB and AP-1 contribute to the enhanced glioma survival, radioresistance, and chemoresistance. Curcumin, which may inhibit these pathways, was therefore investigated for a potential therapeutic role in glioma. The effect of curcumin on glioma survival was investigated in human (T98G, U87MG, and T67) and rat (C6) glioma cell lines. The ability of curcumin to overcome glioma cell radioresistance and chemoresistance was also explored. Curcumin reduced cell survival in a p53- and caspase-independent manner, an effect correlated with the inhibition of AP-1 and NFκB signaling pathways via prevention of constitutive JNK and Akt activation. Curcumin-sensitized glioma cells to several clinically utilized chemotherapeutic agents (cisplatin, etoposide, camptothecin, and doxorubicin) and radiation, effects correlated with reduced expression of bcl-2 and IAP family members as well as DNA repair enzymes (MGMT, DNA-PK, Ku70, Ku80, and ERCC-1). These findings support a role for curcumin as an adjunct to traditional chemotherapy and radiation in the treatment of brain cancer.

Original languageEnglish (US)
Pages (from-to)522-538
Number of pages17
JournalJournal of Neurochemistry
Volume102
Issue number2
DOIs
StatePublished - Jul 1 2007

Fingerprint

Curcumin
Transcription Factor AP-1
Glioblastoma
Glioma
Growth
Tumors
Brain
Brain Neoplasms
Cells
DNA Repair Enzymes
Radiation
Camptothecin
Chemotherapy
Radiation effects
Etoposide
Aptitude
Caspases
Survival
Radiation Effects
Doxorubicin

Keywords

  • AP-1
  • Akt
  • Astrocyte
  • Chemotherapy
  • Glioma
  • NFκB
  • Radiation
  • c-Jun N-terminal kinase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

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title = "Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NFκB transcription factors",
abstract = "Malignant gliomas are a debilitating class of brain tumors that are resistant to radiation and chemotherapeutic drugs, contributing to the poor prognosis associated with these tumors. Over-expression of transcription factors such as NFκB and AP-1 contribute to the enhanced glioma survival, radioresistance, and chemoresistance. Curcumin, which may inhibit these pathways, was therefore investigated for a potential therapeutic role in glioma. The effect of curcumin on glioma survival was investigated in human (T98G, U87MG, and T67) and rat (C6) glioma cell lines. The ability of curcumin to overcome glioma cell radioresistance and chemoresistance was also explored. Curcumin reduced cell survival in a p53- and caspase-independent manner, an effect correlated with the inhibition of AP-1 and NFκB signaling pathways via prevention of constitutive JNK and Akt activation. Curcumin-sensitized glioma cells to several clinically utilized chemotherapeutic agents (cisplatin, etoposide, camptothecin, and doxorubicin) and radiation, effects correlated with reduced expression of bcl-2 and IAP family members as well as DNA repair enzymes (MGMT, DNA-PK, Ku70, Ku80, and ERCC-1). These findings support a role for curcumin as an adjunct to traditional chemotherapy and radiation in the treatment of brain cancer.",
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