Capsaicin-induced apoptosis and reduced release of reactive oxygen species in MBT-2 murine bladder tumor cells
Capsaicin-induced apoptosis and reduced release of reactive oxygen species in MBT-2 murine bladder tumor cells
复制标题
DOI：
10.1007/bf02975121
复制
发表时间：
2004-11-01
影响因子：
6.7
通讯作者：
Kim, JA
中科院分区：
文献类型：
--
作者：
Lee, JS;Chang, JS;Kim, JA
膀胱癌是一种常见的癌症，具有很高的复发和死亡率。为防止肿瘤复发和进展，需在经尿路切除后行膀胱内化疗。已知抗氧化剂增强卡介苗(BCG)的抗肿瘤作用，卡介苗是治疗膀胱癌最有效的药物。辣椒素是辣椒属的主要刺激性成分，最近被尝试作为治疗膀胱过度活动的膀胱内药物，它还被证明能诱导许多癌细胞凋亡。在本研究中，我们研究了辣椒素对MBT-2小鼠膀胱肿瘤细胞的诱导凋亡作用及其细胞氧化还原状态的变化。辣椒素以时间和剂量依赖的方式诱导MBT-2细胞死亡。辣椒素诱导的细胞凋亡可被广谱caspase抑制剂Z-VAD-fmk或caspase-3抑制剂Ac-DEVD-CHO阻断。辣椒素除激活caspase-3外，还可诱导细胞色素c的释放，降低细胞内Bcl2蛋白的表达，但对Bax的表达无明显影响。此外，辣椒素在诱导细胞凋亡的浓度下，还能显著降低细胞内活性氧水平和脂质过氧化作用，提示辣椒素可增强卡介苗在膀胱癌治疗中的抗肿瘤作用。这些结果进一步表明辣椒素可能是一种有价值的膀胱癌化疗药物。
Bladder cancer is a common cancer with high risk of recurrence and mortality. Intravesicle chemotherapy after trans-urethral resection is required to prevent tumor recurrence and progression. It has been known that antioxidants enhance the antitumor effect of bacillus Calmette-Guerin (BCG), the most effective intravesical bladder cancer treatment. Capsaicin, the major pungent ingredient in genus Capsicum, has recently been tried as an intravesical drug for overactive bladder and it has also been shown to induce apoptotic cell death in many cancer cells. In this study, we investigated the apoptosis-inducing effect and alterations in the cellular redox state of capsaicin in MBT-2 murine bladder tumor cells. Capsaicin induced apoptotic MBT-2 cell death in a time- and dose-dependent manner. The capsaicin-induced apoptosis was blocked by the pretreatment with Z-VAD-fmk, a broad-range caspase inhibitor, or Ac-DEVD-CHO, a caspase-3 inhibitor. In addition to the caspase-3 activation, capsaicin also induced cytochrome c release and decrease in Bcl-2 protein expression with no changes in the level of Bax. Furthermore, capsaicin at the concentration of inducing apoptosis also markedly reduced the level of reactive oxygen species and lipid peroxidation, implying that capsaicin may enhance the antitumor effect of BCG in bladder cancer treatment. These results further suggest that capsaicin may be a valuable intravesical chemotherapeutic agent for bladder cancers.