HOI-02 induces apoptosis and G2-M arrest in esophageal cancer mediated by ROS

C. Zhang, K. Liu, K. Yao, K. Reddy, Y. Zhang, Y. Fu, G. Yang, T. A. Zykova, S. H. Shin, H. Li, J. Ryu, Y. N. Jiang, X. Yin, W. Ma, A. M. Bode, Z. Dong, Z. Dong

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Reactive oxygen species (ROS) are chemically reactive molecules that perform essential functions in living organisms. Accumulating evidence suggests that many types of cancer cells exhibit elevated levels of ROS. Conversely, generation of ROS has become an effective method to kill cancer cells. (E)-3-hydroxy-3-(4-(4-nitrophenyl)-2-oxobut-3-en-1-yl) indolin-2-one, which is an NO2 group-containing compound designated herein as HOI-02, generated ROS and, in a dose-dependent manner, decreased esophageal cancer cell viability and inhibited anchorage-independent growth, followed by apoptosis and G2-M arrest. Moreover, results of an in vivo study using a patient-derived xenograft mouse model showed that HOI-02 treatment suppressed the growth of esophageal tumors, without affecting the body weight of mice. The expression of Ki-67 was significantly decreased with HOI-02 treatment. In addition, the phosphorylation of c-Jun, and expression of p21, cleaved caspase 3, and DCFH-DA were increased in the HOI-02-treated group compared with the untreated control group. In contrast, treatment of cells with (E)-3-(4-(4-aminophenyl)-2-oxobut-3-en-1-yl)-3-hydroxyindolin-2-one, which is an NH2 group-containing compound designated herein as HOI-11, had no effect. Overall, we identified HOI-02 as an effective NO2 group-containing compound that was an effective therapeutic or preventive agent against esophageal cancer cell growth.

Original languageEnglish (US)
Article numbere1912
JournalCell Death and Disease
Volume6
Issue number10
DOIs
StatePublished - Oct 1 2015

Bibliographical note

Funding Information:
Acknowledgements. We thank Todd Schuster for technical assistance with flow cytometry, Alyssa Langfald for TUNEL assay and Nicki Brickman for assistance in submitting our manuscript. This work was supported by National Institutes of Health grants CA172457, CA166011, R37CA081064 and The Hormel Foundation.

Publisher Copyright:
© 2015 Macmillan Publishers Limited All rights reserved 2041-4889/15.

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