Issue 25, 2015

Identification of nitric oxide-releasing derivatives of oleanolic acid as potential anti-colon cancer agents

Abstract

A group of nitric oxide (NO)-releasing derivatives of oleanolic acid (OA) (5–13) were designed, synthesized and biologically evaluated for their anti-colon cancer activity. It was found that the most potent compound 6 preferably released high levels of NO in colon cancer cells but not in normal cells, leading to potent cytotoxicity against colon cancer cells. In addition, 6 was more prone to produce NO catalyzed by GSTπ relative to GSTα. Furthermore, 6 significantly inhibited the tumor growth in a mouse xenograft model. Finally, 6 induced nitration of tyrosine residues in mitochondrial protein, down-regulated Wnt/β-catenin pathway, and inhibited COX-2 centered signaling loop in colon cancer cells. Collectively, our findings suggested that 6 could be a promising candidate for the intervention of colon cancer.

Graphical abstract: Identification of nitric oxide-releasing derivatives of oleanolic acid as potential anti-colon cancer agents

Supplementary files

Article information

Article type
Paper
Submitted
07 Jan 2015
Accepted
11 Feb 2015
First published
12 Feb 2015

RSC Adv., 2015,5, 19445-19454

Author version available

Identification of nitric oxide-releasing derivatives of oleanolic acid as potential anti-colon cancer agents

J. Fu, Y. Zou, Z. Huang, C. Yan, Q. Zhou, H. Zhang, Y. Lai, S. Peng and Y. Zhang, RSC Adv., 2015, 5, 19445 DOI: 10.1039/C5RA00270B

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