TY - JOUR
T1 - Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NFκB transcription factors
AU - Dhandapani, Krishnan M.
AU - Mahesh, Virendra B.
AU - Brann, Darrell W.
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
KW - AP-1
KW - Akt
KW - Astrocyte
KW - Chemotherapy
KW - Glioma
KW - NFκB
KW - Radiation
KW - c-Jun N-terminal kinase
UR - http://www.scopus.com/inward/record.url?scp=34347221946&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34347221946&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2007.04633.x
DO - 10.1111/j.1471-4159.2007.04633.x
M3 - Article
C2 - 17596214
AN - SCOPUS:34347221946
SN - 0022-3042
VL - 102
SP - 522
EP - 538
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 2
ER -