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Antitumor Activity of a 5-Hydroxy-1H-Pyrrol-2-(5H)-One-Based Synthetic Small Molecule In Vitro and In Vivo.
- Source :
- PLoS ONE; Jun2015, Vol. 10 Issue 6, p1-15, 15p
- Publication Year :
- 2015
-
Abstract
- Alternative chemo-reagents are in great demand because chemotherapy resistance is one of the major challenges in current cancer treatment. 5-hydoxy-1H-pyrrol-2-(5H)-one is an important N-heterocyclic scaffold that is present in natural products and medicinal chemistry. However, its antitumor activity has not been systematically explored. In this study, we screened a panel of 5-hydoxy-1H-pyrrol-2-(5H)-one derivatives and identified compound 1d as possessing strong anti-proliferative activity in multiple cancer cell lines. Cell cycle analysis revealed that 1d can induce S-phase cell cycle arrest and that HCT116 was sensitive to 1d-induced apoptosis. Further analysis indicated that 1d preferentially induced DNA damage and p53 activation in HCT116 cells and that 1d-induced apoptosis is partly dependent on p53. Furthermore, we showed that 1d significantly suppressed tumor growth in xenograft tumor models in vivo. Taken together, our results suggest that 5-hydoxy-1H-pyrrol-2-(5H)-one derivatives bear potential antitumor activity and that 1d is an effective agent for cancer treatment. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 10
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 103567337
- Full Text :
- https://doi.org/10.1371/journal.pone.0128928