Justicidin A decreases the level of cytosolic Ku70 leading to apoptosis in human colorectal cancer cells

Jenq Chang Lee, Chao Hung Lee, Chun Li Su, Chung Wei Huang, Hsiao Sheng Liu, Chun Nan Lin, Shen Jeu Won

研究成果: 雜誌貢獻文章

50 引文 斯高帕斯(Scopus)

摘要

The natural product justicidin A, an arylnaphthalide lignan isolated from Justicia procumbens, significantly inhibited the growth of human colorectal cancer cells HT-29 and HCT 116 at day 6 post-treatment. Further study revealed that justicidin A-treated HT-29 and HCT 116 colorectal cancer cells died of apoptosis. Justicidin A treatment caused DNA fragmentation and an increase in phosphatidylserine exposure of the cells. The number of cells in the sub-G1 phase was also increased upon justicidin A treatment. Caspase-9 but not caspase-8 was activated, suggesting that justicidin A treatment damaged mitochondria. The mitochondrial membrane potential was altered and cytochrome c and Smac were released from mitochondria to the cytoplasm upon justicidin A treatment. The level of Ku70 in the cytoplasm was decreased, but that of Bax in mitochondria was increased by justicidin A. Since Ku70 normally binds and sequesters Bax, these results suggest that justicidin A decreases the level of Ku70 leading to translocation of Bax from the cytosol to mitochondria to induce apoptosis. Oral administration of justicidin A was shown to suppress the growth of HT-29 cells transplanted into NOD-SCID mice, suggesting chemotherapeutic potential of justicidin A on colorectal cancer cells.

原文英語
頁(從 - 到)1716-1730
頁數15
期刊Carcinogenesis
26
發行號10
DOIs
出版狀態已發佈 - 2005 十月 1

ASJC Scopus subject areas

  • Cancer Research

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