The p53-, Bax- and p21-dependent inhibition of colon cancer cell growth by 5-hydroxy polymethoxyflavones
Article first published online: 23 NOV 2010
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 55, Issue 4, pages 613–622, April 2011
How to Cite
Qiu, P., Guan, H., Dong, P., Li, S., Ho, C.-T., Pan, M.-H., McClements, D. J. and Xiao, H. (2011), The p53-, Bax- and p21-dependent inhibition of colon cancer cell growth by 5-hydroxy polymethoxyflavones. Mol. Nutr. Food Res., 55: 613–622. doi: 10.1002/mnfr.201000269
- Issue published online: 4 APR 2011
- Article first published online: 23 NOV 2010
- Manuscript Accepted: 23 SEP 2010
- Manuscript Revised: 5 SEP 2010
- Manuscript Received: 11 JUN 2010
- NIH. Grant Number: CA139174
- Healey Endowment Research Grant
- CVIP grant
- University of Massachusetts Amherst
- Center for Excellence in Apoptosis Research at the Pioneer Valley Life Sciences Institute
- University of Massachusetts, Amherst
- Colon cancer;
- 5-Hydroxy polymethoxyflavones;
Scope: Previously, we reported that 5-hydroxy polymethoxyflavones (5OH-PMFs) isolated from orange, namely 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone, 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone (5HHMF) and 5-hydroxy-6,7,8,4′-tetramethoxyflavone (5HTMF), potently induced apoptosis and cell-cycle arrest in multiple human colon cancer cells. Herein, using isogenic variants of HCT116 human colon cancer cells, we investigated the effects of p53, Bax and p21 on the apoptosis and cell-cycle arrest induced by different 5OH-PMFs.
Methods and results: Annexin V/PI co-staining assay demonstrated that 5HHMF and 5HTMF significantly induced apoptosis in HCT116 (p53+/+) cells but not in HCT116 (p53−/−) cells. Furthermore, 5HHMF and 5HTMF significantly induced apoptosis in HCT116 (Bax+/−) cells, whereas their pro-apoptotic effects on HCT116 (Bax−/−) cells were marginal. All three 5OH-PMFs increased G0/G1 cell population of HCT116 (p53+/+) cells, and these effects were abolished in HCT116 (p53−/−) and HCT116 (p21−/−) cells. Immunoblotting analysis showed that 5HHMF and 5HTMF increased the levels of cleaved caspase-3, cleaved PARP in both HCT116 (p53+/+) and HCT116 (Bax+/−) cells and these effects were much weaker in HCT116 (p53−/−) and HCT116 (Bax−/−) cells.
Conclusion: Our results demonstrated that 5OH-PMFs, especially 5HHMF and 5HTMF, induce apoptosis and cell-cycle arrest by p53-, Bax- and p21-dependent mechanism.