RNase MC2: a new Momordica charantia ribonuclease that induces apoptosis in breast cancer cells associated with activation of MAPKs and induction of caspase pathways
RNase MC2: a new Momordica charantia ribonuclease that induces apoptosis in breast cancer cells associated with activation of MAPKs and induction of caspase pathways
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DOI：
10.1007/s10495-011-0684-z
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发表时间：
2012-04-01
期刊：
影响因子：
7.2
通讯作者：
Tzi Bun Ng
中科院分区：
文献类型：
--
作者：
Fang, Evandro Fei;Zhang, Chris Zhi Yi;Tzi Bun Ng
核糖核酸酶（RNase）是广泛分布的将RNA切割成较小片段的核酸酶。基于其具体的体外和体内抗肿瘤活性，它们是用于不同癌症的有希望的药物。在这里，我们报告的第一次纯化和表征的14 kDa的核糖核酸酶，命名为核糖核酸酶MC 2，在苦瓜种子（苦瓜charantia）。RNase MC 2表现出对面包酵母tRNA、肿瘤细胞rRNA的有效RNA切割活性，以及对尿苷的绝对特异性。RNase MC 2对MCF-7乳腺癌细胞表现出细胞生长抑制和细胞毒活性。用RNase MC 2处理MCF-7细胞引起核损伤（核碎裂、染色质凝聚和DNA片段化），最终导致早期/晚期凋亡。进一步的分子生物学研究表明，RNase MC 2可诱导MAPK（p38、JNK和ERK）和Akt的差异活化。另一方面，RNase MC 2暴露激活caspase-8、caspase-9、caspase-7，增加巴克的产生并切割PARP，这反过来又有助于凋亡反应。总之，RNase MC 2是一种潜在的药物，可以在全球范围内与乳腺癌作斗争。
Ribonucleases (RNases) are ubiquitously distributed nucleases that cleave RNA into smaller pieces. They are promising drugs for different cancers based on their concrete antitumor activities in vitro and in vivo. Here we report for the first time purification and characterization of a 14-kDa RNase, designated as RNase MC2, in the seeds of bitter gourd (Momordica charantia). RNase MC2 manifested potent RNA-cleavage activity toward baker's yeast tRNA, tumor cell rRNA, and an absolute specificity for uridine. RNase MC2 demonstrated both cytostatic and cytotoxic activities against MCF-7 breast cancer cells. Treatment of MCF-7 cells with RNase MC2 caused nuclear damage (karyorrhexis, chromatin condensation, and DNA fragmentation), ultimately resulting in early/late apoptosis. Further molecular studies unveiled that RNase MC2 induced differential activation of MAPKs (p38, JNK and ERK) and Akt. On the other hand, RNase MC2 exposure activated caspase-8, caspase-9, caspase-7, increased the production of Bak and cleaved PARP, which in turn contributed to the apoptotic response. In conclusion, RNase MC2 is a potential agent which can be exploited in the worldwide fight against breast cancer.