PMID- 18593936
OWN - NLM
STAT- MEDLINE
DCOM- 20080805
LR  - 20240312
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 68
IP  - 13
DP  - 2008 Jul 1
TI  - Curcumin decreases specificity protein expression in bladder cancer cells.
PG  - 5345-54
LID - 10.1158/0008-5472.CAN-07-6805 [doi]
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 micromol/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 
      kappaB (NF-kappaB)-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.
FAU - Chadalapaka, Gayathri
AU  - Chadalapaka G
AD  - Department of Veterinary Physiology and Pharmacology, Texas A&M University, 
      College Station, Texas 77843-4466, USA.
FAU - Jutooru, Indira
AU  - Jutooru I
FAU - Chintharlapalli, Sudhakar
AU  - Chintharlapalli S
FAU - Papineni, Sabitha
AU  - Papineni S
FAU - Smith, Roger 3rd
AU  - Smith R 3rd
FAU - Li, Xiangrong
AU  - Li X
FAU - Safe, Stephen
AU  - Safe S
LA  - eng
GR  - P30 ES009106/ES/NIEHS NIH HHS/United States
GR  - P30 ES009106-09/ES/NIEHS NIH HHS/United States
GR  - ES09106/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Sp Transcription Factors)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/pharmacology/therapeutic use
MH  - Cell Cycle/drug effects/genetics
MH  - Curcumin/*pharmacology/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation/drug effects
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - RNA, Small Interfering/pharmacology
MH  - Sp Transcription Factors/antagonists & inhibitors/*genetics
MH  - Time Factors
MH  - Tumor Burden/drug effects
MH  - Tumor Cells, Cultured
MH  - Urinary Bladder Neoplasms/*drug therapy/*genetics/pathology
MH  - Xenograft Model Antitumor Assays
PMC - PMC2587449
MID - NIHMS56320
EDAT- 2008/07/03 09:00
MHDA- 2008/08/06 09:00
PMCR- 2009/07/01
CRDT- 2008/07/03 09:00
PHST- 2008/07/03 09:00 [pubmed]
PHST- 2008/08/06 09:00 [medline]
PHST- 2008/07/03 09:00 [entrez]
PHST- 2009/07/01 00:00 [pmc-release]
AID - 68/13/5345 [pii]
AID - 10.1158/0008-5472.CAN-07-6805 [doi]
PST - ppublish
SO  - Cancer Res. 2008 Jul 1;68(13):5345-54. doi: 10.1158/0008-5472.CAN-07-6805.