Predominant enhancement of apoptosis induced by methyl jasmonate in bladder cancer cells: therapeutic effect of the Antp-conjugated Smac peptide

Predominant enhancement of apoptosis induced by methyl jasmonate in bladder cancer cells: therapeutic effect of the Antp-conjugated Smac peptide
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茉莉酸甲酯诱导膀胱癌细胞凋亡的显着增强:Antp 缀合的 Smac 肽的治疗作用

DOI:
10.1097/cad.0b013e3283482d40
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发表时间:
2011-10
期刊:
影响因子:
2.3
通讯作者:
Fuqing Zeng
Fuqing Zeng
中科院分区:
医学4区
文献类型:
--
作者:
Xingyuan Xiao;Guosong Jiang;Liang Wang;Lei Lv;Fuqing Zeng

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茉莉酸甲酯(MJ)作为一种很有前途的抗肿瘤化合物,最近引起了人们的注意,因为它在广泛的恶性肿瘤中具有高度特异性的促凋亡特性。然而,实现治疗益处所需的高剂量限制了其临床开发。在这里,我们假设凋亡抑制蛋白(IAP)家族可以抑制MJ介导的癌细胞凋亡。我们将MJ与IAPs抑制剂(第二种来源于胱天蛋白酶的激活剂(Smac)肽)组合来治疗膀胱癌细胞。结果表明,MJ和Smac肽联合通过释放和激活IAP结合的caspase-3,以协同方式增强了细胞凋亡诱导作用。这些发现表明,抑制IAP可以克服癌细胞对MJ的抗性。
Methyl jasmonate (MJ) has recently attracted attention as a promising antitumoral compound because of its highly specific proapoptotic properties in a wide range of malignancies. However, the high doses required to achieve a therapeutic benefit have limited its clinical development. Here, we hypothesize that the family of inhibitor of apoptosis proteins (IAPs) may inhibit MJ-mediated apoptosis in cancer cells. We combined MJ with the IAPs inhibitor, the second mitochondria-derived activator of caspases (Smac) peptide to treat bladder cancer cells. The results showed that the combination of MJ and Smac peptide enhanced the apoptosis-inducing effect in a synergistic manner by releasing and activating IAPs-bounding caspase-3. These findings suggest that the inhibition of IAPs could overcome the resistance of cancer cells to MJ.
DOI: 10.1002/chin.201007277
发表时间: 2010-02
期刊: ChemInform
影响因子: --
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