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
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
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DOI：
10.1158/1535-7163.mct-06-0545
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发表时间：
2007-03-01
影响因子：
5.7
通讯作者：
Aggarwal, Bharat B.
中科院分区：
文献类型：
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作者：
Kamat, Ashish M.;Sethi, Gautam;Aggarwal, Bharat B.
不同国家的膀胱癌死亡率有所不同；西方国家的膀胱癌死亡率最高，而印度等东方国家的膀胱癌死亡率最低。在美国等富裕国家，吸烟是膀胱癌的主要风险因素之一。局限性早期膀胱癌的治疗方法是切除和膀胱内细胞因子治疗，而转移性膀胱癌的治疗通常采用不同的全身化疗组合。姜黄素，一种在印度等国家普遍消费的黄色咖喱色素，是否在预防或治疗膀胱癌方面具有任何作用。我们发现姜黄素抑制干扰素-α敏感(RT4V6)和干扰素耐药(KU-7)膀胱癌细胞的增殖、诱导细胞周期停滞和DNA片段化。姜黄素还可增强化疗药物(吉西他滨和紫杉醇)以及细胞因子[肿瘤坏死因子(TNF)和肿瘤坏死因子相关的凋亡诱导配体]的凋亡作用。姜黄素的这种作用与对干扰素-α的敏感性和耐药性无关，干扰素-α通常用于治疗膀胱癌。研究了姜黄素的作用是否通过调节核因子-kappaB(NF-kappa B)途径来实现。吉西他滨和肿瘤坏死因子都激活了膀胱癌细胞中的核因子-kappaB，而姜黄素抑制了这种激活。同样，吸烟是膀胱癌的主要风险因素，也激活了核因子-kappaB，而姜黄素抑制了它。香烟烟雾诱导的核因子-kappaB调控基因产物环氧合酶-2和血管内皮生长因子的表达分别与增殖和血管生成有关，姜黄素也下调这两种基因的表达。
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-alpha-sensitive (RT4V6) and IFN-alpha-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-alpha, commonly used for treatment of bladder cancer. Whether the effects of curcumin are mediated through modulation of the nuclear factor-kappa B (NF-kappa B) pathway known to mediate antiapoptosis was investigated. Both gemcitabine and TNF activated NF-kappa B in bladder cancer cells and curcumin suppressed this activation. Similarly, cigarette smoke, a major risk factor for bladder cancer, also activated NF-kappa B and curcumin suppressed it. Cigarette smoke-induced expression of the NF-kappa B-regulated gene products cyclooxygenase-2 and vascular endothelial growth factor, linked with proliferation and angiogenesis, respectively, was also down-regulated by curcumin.