Cribrostatin 6 induces death in cancer cells through a reactive oxygen species (ROS)-mediated mechanism

被引:28
|
作者
Hoyt, Mirth T. [1 ]
Palchaudhuri, Rahul [1 ]
Hergenrother, Paul J. [1 ]
机构
[1] Univ Illinois, Dept Chem, Roger Adams Lab, Urbana, IL 61801 USA
关键词
Cribrostatin; 6; ROS; Quiescent; 3T3; Quinone; HMOX1; Apoptosis; Cancer stem cells; Transcript profile; Quiescent cells; Drug-resistant cell lines; DNA TOPOISOMERASE-II; SPONGE CRIBROCHALINA SP; SOLID TUMORS; STEM-CELLS; ANTINEOPLASTIC AGENTS; MOLECULAR-MECHANISMS; ANTITUMOR-ACTIVITY; ANTICANCER AGENTS; INDUCED APOPTOSIS; OXIDATIVE STRESS;
D O I
10.1007/s10637-010-9390-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cribrostatin 6 is a quinone-containing natural product that induces the death of cancer cell lines in culture, and its mechanism of action and scope of activity are unknown. Here we show that cribrostatin 6 has broad anticancer activity, potently inducing apoptotic cell death that is not preceded by any defined cell cycle arrest. Consistent with this data, we find that cribrostatin 6 treated cells have large amounts of reactive oxygen species (ROS) and, based on transcript profiling experiments and other data, this ROS generation is likely the primary mechanism by which cribrostatin 6 induces apoptosis. Given the success of certain ROS producers as anticancer agents, cribrostatin 6 has potential as a novel chemotherapeutic agent.
引用
收藏
页码:562 / 573
页数:12
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