TY - JOUR
T1 - Curcumin potentiates the apoptotic effects of chemotherapeutic agents and cytokines through down-regulation of nuclear factor-κB and nuclear factor-κB-regulated gene products in IFN-α-sensitive and IFN-α-resistant human bladder cancer cells
AU - Kamat, Ashish M.
AU - Sethi, Gautam
AU - Aggarwal, Bharat B.
PY - 2007/3
Y1 - 2007/3
N2 - Bladder cancer mortality varies between the countries; whereas being highest in Western countries, it is lowest in Eastern countries, such as India. Cigarette smoking is one of the major risk factors for bladder cancer in affluent nations, such as United States. Localized early-stage bladder cancer is treated with resection and intravesical cytokine therapy, whereas metastatic cancer is typically treated with various combinations of systemic chemotherapy. Whether curcumin, a yellow curry pigment commonly consumed in countries, such as India, has any role in prevention or treatment of bladder cancer was investigated. We found that curcumin inhibited the proliferation, induced cell cycle arrest, and DNA fragmentation in both IFN-α-sensitive (RT4V6) and IFN-α-resistant (KU-7) bladder cancer cells. Curcumin also potentiated the apoptotic effects of the chemotherapeutic agents (gemcitabine and paclitaxel) and of cytokines [tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand]. This effect of curcumin was independent of sensitivity and resistance to IFN-α, commonly used for treatment of bladder cancer. Whether the effects of curcumin are mediated through modulation of the nuclear factor-κB (NF-κB) pathway known to mediate antiapoptosis was investigated. Both gemcitabine and TNF activated NF-κB in bladder cancer cells and curcumin suppressed this activation. Similarly, cigarette smoke, a major risk factor for bladder cancer, also activated NF-κB and curcumin suppressed it. Cigarette smoke-induced expression of the NF-κB-regulated gene products cyclooxygenase-2 and vascular endothelial growth factor, linked with proliferation and angiogenesis, respectively, was also down-regulated by curcumin.
AB - Bladder cancer mortality varies between the countries; whereas being highest in Western countries, it is lowest in Eastern countries, such as India. Cigarette smoking is one of the major risk factors for bladder cancer in affluent nations, such as United States. Localized early-stage bladder cancer is treated with resection and intravesical cytokine therapy, whereas metastatic cancer is typically treated with various combinations of systemic chemotherapy. Whether curcumin, a yellow curry pigment commonly consumed in countries, such as India, has any role in prevention or treatment of bladder cancer was investigated. We found that curcumin inhibited the proliferation, induced cell cycle arrest, and DNA fragmentation in both IFN-α-sensitive (RT4V6) and IFN-α-resistant (KU-7) bladder cancer cells. Curcumin also potentiated the apoptotic effects of the chemotherapeutic agents (gemcitabine and paclitaxel) and of cytokines [tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand]. This effect of curcumin was independent of sensitivity and resistance to IFN-α, commonly used for treatment of bladder cancer. Whether the effects of curcumin are mediated through modulation of the nuclear factor-κB (NF-κB) pathway known to mediate antiapoptosis was investigated. Both gemcitabine and TNF activated NF-κB in bladder cancer cells and curcumin suppressed this activation. Similarly, cigarette smoke, a major risk factor for bladder cancer, also activated NF-κB and curcumin suppressed it. Cigarette smoke-induced expression of the NF-κB-regulated gene products cyclooxygenase-2 and vascular endothelial growth factor, linked with proliferation and angiogenesis, respectively, was also down-regulated by curcumin.
UR - http://www.scopus.com/inward/record.url?scp=34147138418&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34147138418&partnerID=8YFLogxK
U2 - 10.1158/1535-7163.MCT-06-0545
DO - 10.1158/1535-7163.MCT-06-0545
M3 - Article
C2 - 17363495
AN - SCOPUS:34147138418
SN - 1535-7163
VL - 6
SP - 1022
EP - 1030
JO - Molecular cancer therapeutics
JF - Molecular cancer therapeutics
IS - 3
ER -