TY - JOUR
T1 - Curcumin decreases specificity protein expression in bladder cancer cells
AU - Chadalapaka, Gayathri
AU - Jutooru, Indira
AU - Chintharlapalli, Sudhakar
AU - Papineni, Sabitha
AU - Smith, Roger
AU - Li, Xiangrong
AU - Safe, Stephen
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/7/1
Y1 - 2008/7/1
N2 - Curcumin is the active component of tumeric, and this polyphenolic compound has been extensively investigated as an anticancer drug that modulates multiple pathways and genes. In this study, 10 to 25 μmol/L curcumin inhibited 253JB-V and KU7 bladder cancer cell growth, and this was accompanied by induction of apoptosis and decreased expression of the proapoptotic protein survivin and the angiogenic proteins vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR1). Because expression of survivin, VEGF, and VEGFR1 are dependent on specificity protein (Sp) transcription factors, we also investigated the effects of curcumin on Sp protein expression as an underlying mechanism for the apoptotic and antiangiogenic activity of this compound. The results show that curcumin induced proteasome-dependent down-regulation of Sp1, Sp3, and Sp4 in 253JB-V and KU7 cells. Moreover, using RNA interference with small inhibitory RNAs for Sp1, Sp3, and Sp4, we observed that curcumin-dependent inhibition of nuclear factor κB (NF-κB)-dependent genes, such as bcl-2, survivin, and cyclin D1, was also due, in part, to loss of Sp proteins. Curcumin also decreased bladder tumor growth in athymic nude mice bearing KU7 cells as xenografts and this was accompanied by decreased Sp1, Sp3, and Sp4 protein levels in tumors. These results show for the first time that one of the underlying mechanisms of action of curcumin as a cancer chemotherapeutic agent is due, in part, to decreased expression of Sp transcription factors in bladder cancer cells.
AB - Curcumin is the active component of tumeric, and this polyphenolic compound has been extensively investigated as an anticancer drug that modulates multiple pathways and genes. In this study, 10 to 25 μmol/L curcumin inhibited 253JB-V and KU7 bladder cancer cell growth, and this was accompanied by induction of apoptosis and decreased expression of the proapoptotic protein survivin and the angiogenic proteins vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR1). Because expression of survivin, VEGF, and VEGFR1 are dependent on specificity protein (Sp) transcription factors, we also investigated the effects of curcumin on Sp protein expression as an underlying mechanism for the apoptotic and antiangiogenic activity of this compound. The results show that curcumin induced proteasome-dependent down-regulation of Sp1, Sp3, and Sp4 in 253JB-V and KU7 cells. Moreover, using RNA interference with small inhibitory RNAs for Sp1, Sp3, and Sp4, we observed that curcumin-dependent inhibition of nuclear factor κB (NF-κB)-dependent genes, such as bcl-2, survivin, and cyclin D1, was also due, in part, to loss of Sp proteins. Curcumin also decreased bladder tumor growth in athymic nude mice bearing KU7 cells as xenografts and this was accompanied by decreased Sp1, Sp3, and Sp4 protein levels in tumors. These results show for the first time that one of the underlying mechanisms of action of curcumin as a cancer chemotherapeutic agent is due, in part, to decreased expression of Sp transcription factors in bladder cancer cells.
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U2 - 10.1158/0008-5472.CAN-07-6805
DO - 10.1158/0008-5472.CAN-07-6805
M3 - Article
C2 - 18593936
AN - SCOPUS:48549085442
SN - 0008-5472
VL - 68
SP - 5345
EP - 5354
JO - Cancer research
JF - Cancer research
IS - 13
ER -