Involvement of reactive oxygen species/c-Jun NH(2)-terminal kinase pathway in kotomolide A induces apoptosis in human breast cancer cells.
Involvement of reactive oxygen species/c-Jun NH(2)-terminal kinase pathway in kotomolide A induces apoptosis in human breast cancer cells.
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kotomolide A 中活性氧/c-Jun NH(2)-末端激酶通路的参与可诱导人乳腺癌细胞凋亡。
DOI：
10.1016/j.taap.2008.01.034
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发表时间：
2008
影响因子：
3.8
通讯作者：
Y. Hsu
中科院分区：
文献类型：
--
作者：
Po;Chung;Tz;Chun‐ching Lin;Y. Hsu
我们的研究首次研究了 kotomolide A (KTA) 是一种从樟科肉桂 (Cinnamomum kotoense) 叶子中分离出来的新丁内酯成分，对两种人类乳腺癌细胞系 MCF-7 和 MDA-MB-231 的抗癌作用。 KTA 在癌细胞系中表现出选择性的抗增殖作用，而在正常乳腺上皮细胞中没有表现出任何毒性。用 KTA 处理癌细胞以触发 G2/M 期停滞与 p21/WAF1 水平升高和细胞周期蛋白 A、细胞周期蛋白 B1、cdc2 和 cdc25C 量减少相关。 KTA 通过触发线粒体和死亡受体 5 (DR5) 凋亡途径来诱导癌细胞死亡，但不作用于 Fas 受体。 MCF-7 和 MDA-MB-231 细胞暴露于 KTA 会导致细胞谷胱甘肽减少和 ROS 产生，并伴有 JNK 激活和细胞凋亡。 NAC 和过氧化氢酶这两种抗氧化剂均通过抑制 JNK 磷酸化并随后触发 DR5 细胞死亡途径，显着减少细胞凋亡。 siRNA 减少 JNK 表达可减少 KTA 介导的 Bim 裂解、DR5 上调和细胞凋亡。此外，每日 KTA i.p.皮下注射 MDA-MB-231 裸鼠与媒介物处理的对照相比，肿瘤的平均肿瘤体积减少了 50%。综上所述，数据表明乳腺癌细胞响应 KTA 的细胞死亡依赖于 ROS 的产生和 JNK 的激活，从而触发内在和外在的细胞凋亡途径。 ROS/JNK 通路可能成为乳腺癌化疗新方法的有用靶标。
The anticancer effects of kotomolide A (KTA), a new butanolide constituent isolated from the leaves of Cinnamomum kotoense (Lauraceae), on the two human breast cancer cell lines MCF-7 and MDA-MB-231, were first investigated in our study. KTA exhibited selectively antiproliferative effects in cancer cell lines without showing any toxicity in normal mammary epithelial cells. Treatment of cancer cells with KTA to trigger G2/M phase arrest was associated with increased p21/WAF1 levels and reduced amounts of cyclin A, cyclin B1, cdc2 and cdc25C. KTA induced cancer cell death treatment by triggering mitochondrial and death receptor 5 (DR5) apoptotic pathways, but did not act on the Fas receptor. Exposure of MCF-7 and MDA-MB-231 cells to KTA resulted in cellular glutathione reduction and ROS generation, accompanied by JNK activation and apoptosis. Both antioxidants, NAC and catalase, significantly decreased apoptosis by inhibiting the phosphorylation of JNK and subsequently triggering DR5 cell death pathways. The reduction of JNK expression by siRNA decreased KTA-mediated Bim cleavage, DR5 upregulation and apoptosis. Furthermore, daily KTA i.p. injections in nude mice with MDA-MB-231 s.c. tumors resulted in a 50% decrease of mean tumor volume, compared with vehicle-treated controls. Taken together, the data show that cell death of breast cancer cells in response to KTA is dependent upon ROS generation and JNK activation, triggering intrinsic and extrinsic apoptotic pathways. The ROS/JNK pathway could be a useful target for novel approaches in breast cancer chemotherapy.
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Bcl-2 介导的细胞凋亡抵抗与谷胱甘肽诱导的 AP24 核 DNA 片段激活抑制有关。
DOI：
--
发表时间：
1998
期刊：
Cancer research.
影响因子：
--
作者：
Wright,SC;Wang,H;Wei,QS;Kinder,DH;Larrick,JW
通讯作者：
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影响因子：
11.2
作者：
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通讯作者：
Daniel I. Feig;Thomas M. Reid;Lawrence A. Loeb
影响因子：
11.2
作者：
Zhou, Jun-Ying;Liu, Yusen;Wu, Gen Sheng
通讯作者：
Wu, Gen Sheng
影响因子：
11.2
作者：
Randy Yat Choi Poon;Man Sang Chau;Katsumi Yamashita;Tony Hunter
通讯作者：
Randy Yat Choi Poon;Man Sang Chau;Katsumi Yamashita;Tony Hunter
影响因子：
2.4
作者：
Mu, Jin-Xia;Zhai, Zhi-Wen;Liu, Xing-Hai
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