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Title: Nox4-dependent ROS modulation by amino endoperoxides to induce apoptosis in cancer cells
Authors: Zhu, Pengcheng
Tong, Benny Meng Kiat
Wang, Runze
Chen, Jiapeng
Foo, Selin
Chong, Han Chung
Wang, Xiao Ling
Ang, Gim Yean
Chiba, Shunsuke
Tan, Nguan Soon
Keywords: DRNTU::Science::Biological sciences::Microbiology
Issue Date: 2013
Source: Zhu, P., Tong, B. M. K., Wang, R., Chen, J. P., Foo, S., Chong, H. C., et al. (2013). Nox4-dependent ROS modulation by amino endoperoxides to induce apoptosis in cancer cells. Cell Death and Disease, 4, e552.
Series/Report no.: Cell death and disease
Abstract: Tumor metastasis is the main cause of death in cancer patients. Anoikis resistance is one critical malefactor of metastatic cancer cells to resist current clinical chemotherapeutic treatments. Although endoperoxide-containing compounds have long been suggested as anticancer drugs, few have been clinically employed due to their instability, complex synthesis procedure or low tumor cell selectivity. Herein, we describe a one-pot strategy to synthesize novel amino endoperoxides and their derivatives with good yields and stabilities. In vitro cell-based assays revealed that 4 out of the 14 amino endoperoxides selectively induce metastatic breast carcinoma cells but not normal breast cells to undergo apoptosis, in a dose-dependent manner. Mechanistic studies showed that the most potent amino endoperoxide, 4-Me, is selective for cancer cells expressing a high level of Nox4. The anticancer effects are further shown to be associated with reduced O2−:H2O2 ratio and increased ·OH level in the cancerous cells. Animal study showed that 4-Me impairs orthotopic breast tumor growth as well as tumor cell metastasis to lymph nodes. Altogether, our study suggests that anticancer strategies that focus on redox-based apoptosis induction in tumors are clinically viable.
ISSN: 2041-4889
DOI: 10.1038/cddis.2013.68
Rights: © 2013 Macmillan Publishers Limited. Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
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